m.rolph@garvan.org.au

Arthritis and Asthma Research Program
Garvan Institute of Medical Research
384 Victoria Street
Sydney, NSW 2010
Ph: 9295 8351

Our research group aims to identify novel genes that control inflammatory disease, with the ultimate goal being to develop new drugs for these diseases. The 2 Hons projects offered in 2007 involve molecular analysis of ‘candidate’ asthma genes.

Project 1: Lipids and the inflammatory response in asthma

Fatty acid binding proteins (FABPs) are cytoplasmic proteins involved in lipid transport and metabolism. We have recently discovered that FABPs are key regulators of the inflammatory response in asthma. The key question is: how do lipids regulate the inflammatory response? This project will test our hypothesis that FABPs control lipid-regulated intracellular signalling pathways. To do this, inflammatory intracellular signalling pathways (such as those associated with the transcription factors NF-kB and PPAR-gamma) will be measured in dendritic cells and macrophages from FABP ‘knockout’ mice. This will allow us to understand how FABPs control asthma, but will also provide fundamental insight into how lipids can regulate intracellular signalling pathways. This project will use a range of cellular and molecular techniques including cell culture, PCR, western blotting, luciferase reporter assays and ELISA.

• Shum BOV, Mackay CR, Gorgun CZ, Frost M, Kumar RK, Hotamisligil GS, Rolph MS. Requirement for adipocyte fatty acid binding protein aP2 in allergic airway inflammation. J. Clin. Invest. 116:2183-92

Project 2: Analysis of airway gene expression using microarrays

Airway epithelial cells play a major role in regulating inflammation in asthma. To identify new asthma genes, we have performed gene profiling (microarray) experiments on airway epithelial cells treated with cytokines that protect against asthma (interferon-gamma), and cytokines that promote asthma (interleukin-4 and interleukin-13). This project will involve bioinformatic analysis of the array data to identify new candidate genes. Preliminary analysis of the selected genes will then be undertaken. Depending on the genes selected, this project will involve a variety of techniques such as cell culture, bioinformatics, real-time PCR, transient transfections and immunohistochemistry.

• Rolph MS, Sisavanh M, Liu SM, Mackay CR. Clues to asthma pathogenesis from microarray expression studies. Pharmacol Ther. 2006;109:284-294