Evolutionary conservation of caspase regulatory mechanisms [ 2007 - 2009 ]

Research Grant

Researchers: A/Pr Christine Hawkins (Principal investigator)

Brief description Apoptosis is a highly controlled process by which metazoans eliminate unwanted and dangerous cells. Dysregulation of apoptosis can contribute to many conditions including cancer, autoimmune and degenerative diseases. To develop therapeutic reagents that promote cell death when it fails to occur, or prevent it from happening inappropriately, it is necessary to understand the mechanisms controlling apoptosis. To date, many of the important insights into mammalian cell death signalling have been informed by studies of apoptotic pathways in simpler, experimentally tractable model organisms. This project will exploit biochemical approaches and powerful yeast-based tools developed by CI-A to further explore cell death pathways of the nematode Caenorhabditis elegans, and compare these with mammalian apoptosis pathways. Key findings will be verified using genetic approaches. Most apoptotic stimuli ultimately kill mammalian, insect or nematode cells by triggering activation of proteases termed caspases. However, the mechanisms by which caspase activity is regulated appear to differ somewhat between mammals and worms. We will address two general possibilities: either these animals really do differ significantly in the upstream regulation of cell death pathways, or that functional counterparts of key components have not hitherto been identified or fully characterised. Understanding the way in which mammalian apoptosis is regulated will aid in the design of diagnostic and therapeutic reagents for the many diseases in which dysregulation of apoptosis has been implicated. This project seeks to define the extent to which apoptotic regulation is conserved between mammals and nematodes. This knowledge will enable researchers to maximise the utility of nematode cell death models for the further elucidation of mammalian cell death regulatory mechanisms, and to explore how apoptosis can be manipulated for clinical benefit.

Funding Amount $AUD 585,215.08

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant