In vivo and in vitro studies of the Human -308 TNF promoter Polymorphism.

Funded Activity Summary

The identification of genetic variation in region of the DNA that controls expression of the inflammatory cytokine Tumour Necrosis Factor (TNF) and its association with a number of autoimmune and inflammatory diseases, has led to speculation that this genetic difference may play a role in predisposing some people to these diseases. We have isolated an activity, TPF1, that may regulate expression through interaction with this DNA control region. During the tenure of this grant we intend to clarify some of these questions, we will generate genetically modified mice that have either of the two genetic forms of the human TNF promoter. These mice will be compared in two models of associated disease, murine Lupus and cerebral malaria. We will also characterise the interactions of TPF1 with other components of the TNF control region. An understanding of the role of TPF1 in controlling TNF expression and an appreciation of the cell types that are able to express the phenotype, will allow the development of more subtle, cell specific strategies to modulate the activity of TNF without completely abolishing expression and may lead to better preventative and therapeutic strategies.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $232,131.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Gene Expression

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

autoimmune diseases | gene regulation | immunogenetics | infectous diseases | malaria | transcription factors

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