Dr Katharina Gaus, NHF/NHMRC RD Wright Fellow

Cell membranes are complex with over ~1000 different lipid species and numerous membrane proteins. Our research focuses on the structure of celluluar membranes, particular the plasma membrane and how membranes form functional microdomains.

Cholesterol and sphingolipids (predominantly sphingomyelin) form liquid-ordered microdomains or 'lipid rafts' in the plasma membrane of cells. These domains have been generally viewed as ordered clusters of lipids that float, like rafts, in a sea of liquid-disordered lipids, predominantly phospholipids. It is becoming increasingly recognised that such domains play important roles in many cellular functions, including signal transduction and membrane trafficking. In our research we are using macrophages, T lymphocytes and endothelial cells. Our work focuses on the following areas:

• Microscopy tools
We are developing new light microscopy techniques to visualize lipid domains in live cells and in real time. Using a 2-photon microscope we can image membrane fluidity and by doing so characterize the biophysical properties of lipid domains.

• T lymphocytes activation
T lymphocytes become activated via the engagement of the T cell antigen receptor (TCR) to fulfil their functions in immune responses. We aim to understand how the assembly TCR signalling machinery in plasma membrane creates highly ordered lipid domains and analyse the contributions of these domains to T cell activation.

• Macrophage biology
Together with Wendy Jessup, we are currently studying how lipid raft composition, abundance and function are controlled in the macrophage, particularly in response to development of the foam cell phenotype and during phagocytosis (engulfment of foreign particles) by macrophages

• Cell adhesion and migration
Cell migration requires the spatial and temporal segregation of membrane components to define the front and back of the cell. We are using model surfaces to pinpoint the location of focal adhesions (anchoring points of the cell) and are studying the membrane structure at these sites. We are also conducting live cell microscopy experiments to visualise raft domains in migration cells.

Current Grants

• National Heart Foundation (NHF) & National Health & Medical Research Council of Australia (NHMRC) RD Wright Career Development Award to K Gaus.
  
• Australian Research Council (ARC) Discovery Project: Lipid raft and cytoskeleton organization: How membrane domains give cells direction. K Gaus.
  
• ARC Discovery Project: Silicon base photonic crystals for monitoring biomolecular interactions. M Gal, JJ Gooding, K Gaus
  
• National Heart Foundation of Australia Grant in Aid: Lipid rafts in endothelial cells. K Gaus, W Jessup, KA Rye
  

Selected Publications

Gaus K, Zech T, Harder T.
Visualizing membrane microdomains by Laurdan 2-photon microscopy. Mol Membrane Biol. In Press.

Gaus K, Chklovskaia E, Fazekas B, Jessup W, Harder T. (2005)
Formation of condensed membrane domains at T cell activation sites. J Cell Biol. 171. 121-131

Gaus K, Rodriguez M, Ruberu KR, Gelissen I, Kritharides L, Jessup W (2005).
Domain-specific lipid distribution in macrophage plasma membranes. J. Lipid. Res. 46 1526-1538.

Gaus K, Kritharides L, Schmitz G, Boettcher A, Drobnik W, Langmann T, Quinn CM, Death A, Dean RT, Jessup W. (2004)
Apolipoprotein A-1 interaction with plasma membrane lipid rafts control cholesterol export from macrophages. FASEB J. 18, 575-6.

Gaus K, Gratton E, Kable EPW, Jones AS, Gelissen I, Kritharides L, Jessup W. (2003)
Visualizing lipid structure and raft domains in living cells with 2-photon microscopy. Proc. Natl. Acad. Sci. U. S. A. 100, 15554-9.

Gaus K, Gooding JJ, Dean RT, Kritharides L, Jessup W. (2001)
A kinetic model to evaluate cholesterol efflux from THP-1 macrophages to apoprotein A-1. Biochemistry. 40(31), 9363-73.

Gaus K, Dean RT, Kritharides L, Jessup W. (2001)
Inhibition of cholesterol efflux by 7-ketocholesterol: a comparison between cells, plasma membrane vesicles and liposomes as cholesterol donors. Biochemistry. 40(43), 13002-14.