Autophagy is a process by which all eukaryotic cells degrade (or turnover) parts of their internal structure including organelles that occurs in a specialized compartment of cells - the vacuole (in yeast) or the lysosome (in mammals). In yeast, autophagy is mainly involved in cellular homeostasis (removal of damaged organelles) and adaptation to starvation, but in multicellular organisms (mammals) it is involved in a variety of additional processes such as programmed cell death and development of different tissue-specific functions. Alterations in the levels of autophagy are linked to a growing number of pathological conditions including neurodegenerative diseases such Parkinson's, myopathies, some forms of cancer, and infection by pathogenic bacteria or viruses.

Current work

Selective autophagy of cellular organelles. The turnover of mitochondria, the nucleus and other organelles by autophagy presumably serves as a means of quality control for organelle function. Mechanistically distinct forms of autophagy have been identified. However, the molecular details and regulation of these processes and how they relate to organelle turnover are only now becoming understood. We are using fluorescent protein technology, together with other biochemical and molecular techniques, in yeast and mammalian cells to monitor turnover. This approach is providing new insights into the pathways and molecular mechanisms by which organelle autophagy occurs.

Host-cell response to bacterial infection. Successful microbial pathogens have evolved strategies to avoid or subvert autophagy thereby ensuring their survival within cells. We are looking at the molecular mechanisms by which the soil bacterium, Burkholderia pseudomallei, achieves the avoidance or subversion of autophagy. In humans, infection leads to Melioidosis, a disease endemic in tropical and subtropical areas, including northern Australia. It is also a significant pathogen in many animals. We are investigating the role played by autophagy in the intracellular life-cycle of B. pseudomallei. Our studies have shown that in response to infection of macrophage-like cell line RAW 264.7, the autophagy marker protein LC3 is actually recruited directly to bacteria-containing phagosomes (a process designated LC3-associated phagocytosis; LAP). However, most of the infecting bacteria escaped from phagosome and do not succumb to autophagy. Current and future studies are directed towards the mechanistic basis of the bacterium's ability to avoid autophagy.