The main focus of this research is to define the functional properties and the regulation of a new class of immuno-regulatory receptors termed as Leukocyte immunoglobulin-like receptors (LIRs). In addition, the research aims to identify the as-yet-unknown ligands for these molecules. We and our collaborators in the US have recently published several high impact papers demonstrating that LIRs modulate cellular responses through immunoreceptor tyrosine-based inhibitory motifs, or via association with the Fc receptor chain that contains immunoreceptor tyrosine-based activation motifs. We have also demonstrated that an imbalance in the expression of activating and inhibitory LIRs on leucocytes might be a key mechanism in the development of auto-immune diseases such as rheumatoid arthritis in humans. We currently are investigating the function of LIRs on the major cells that are involved in allergic inflammation. Identification and characterisation of natural ligand(s) for these molecules is one of the major aims for an NHMRC funded Project grant awarded this year.
The assay systems used by the group are based on human tissue, human primary cells and human cell lines, and include: flow cytometry, real time PCR, site-directed mutagenesis, ELISA for cytokines, histamine release, EDN assays, BioPlex, Western blot, immunoprecipitations, Immunohistochemistry. As well as radioactive and non-radioactive ligand binding assays. In addition, expression of recombinant proteins in E-coli, baculovirus and mammalian systems is undertaken. Novel in vitro differentiation systems have been developed for cord blood stem cells to generate human mast cells, myeloid cells and fibroblasts. Tandem mass spectrometry is used for identification of unknown protein ligands.