BACKGROUND, SIGNIFICANCE. Though of vital importance, our innate immune defence is not well understood and the mechanisms involved are therefore of immediate interest to medical science. We and others have shown that insects can serve as a good model for such studies. Insects respond rapidly to infection, producing antibacterial and antifungal peptides that are secreted into the blood. The value of Drosophila as a model was proven by the discovery that Toll-like receptors play an important role in human immunity. This discovery was guided by the finding, first made in my lab, that similar receptors can mediate immune responses in Drosophila. In fact, the entire signaling pathways are conserved between insect and man.
AIMS. To explore the basic molecular mechanisms of innate immunity and stress, taking advantage of the possibilities offered by Drosophila as a model system.
WORKING PLAN. We will study three different aspects of the immune response:
1) The peptidoglycan recognition proteins are pattern recognition molecules and their role will be studied by genetic techniques. Human homologs exist.
2) The transcription factor Relish, is a central mediator of the humoral immune response. The activation of this factor involves a novel mechanism of possible general significance. This mechanism will be investigated.
3) The mechanisms of the innate response of blood cells is a virgin field, which will be explored in our system.