It may be ironic, but by ending the life of unwanted or damaged cells during both development and adult homeostasis, apoptosis or programmed cell death becomes an essential part of life itself.

Professor Andreas Strasser and his group at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne are at the forefront of research into apoptosis, with a particular interest in the mechanisms of its regulation.

Strasser and his colleagues have had a significant effect on the field of apoptosis research, including the discovery of quite a few of the genes that regulate it.

They have and continue to study the function of these genes by making genetically altered mice, both knockouts and knock-in mice.

In fact, Strasser and colleagues have knocked out the largest number of these genes of anyone in the world.

At the ASI meeting, Strasser will talk about the relationship between autoimmunity and some of the genes involved in apoptosis.

"We found out a long time ago that knocking out certain pro-apoptotic genes or abnormally increased expression of anti-apoptotic genes can lead to systemic autoimmune disease in our mice, generally one similar to lupus in humans," Strasser says.

"Recently, we have been studying mechanisms used by the immune system to turn off activation, for example once a pathogen has been successfully cleared. It is important to shut these responses off because a constantly activated immune response can cause unwanted destruction of healthy and normally functioning tissues. I will discuss two aspects of this work at the conference."

Initially, Strasser's group looked for possible mechanisms or pathways mediating cell death within normal tissue with the idea of blocking the destruction in the presence of an overactive immune system, such as in chronic autoimmunity.

Strasser became interested particularly in collateral damage to hepatocytes in the liver, based on evidence from human patients and animal models where fatal destruction of the liver is induced by over-activating either the innate or adaptive immune response.

It remained entirely unclear (prior to their work) how these hepatocytes die, mechanistically, in those circumstances.

"We had a number of suspicions, and it turns out that much of the damage to hepatocytes is mediated by signalling from tumour necrosis factor (TNF) and its receptor, TNFR1, in humans and animal models," Strasser says.

TNFR1 is a classical 'death receptor' for programmed cell death. It has an intracellular death domain and can activate the classical apoptotic pathway.

In addition, the group's findings implicated the protein, Bid, a well-known initiator of apoptosis that can be activated by 'death receptors' in this pathological cell death.

Thus, Strasser made Bid-knockout mice with liver damage and showed conclusively that Bid on its own protects the hepatocytes to some extent - it reduces the pathology - but it does not prevent it and most Bid-knockout mice still die.

Seeking the other factors involved, Strasser followed an educated hunch and first tested Bim, a close relative of Bid, as the other player in apoptosis initiation.

"We made double knock-outs for Bid and Bim, and this produced mice that were entirely resistant to liver destruction. Instead of 100 per cent mice dying, we now had almost all surviving - quite a stunning difference.

"We are just finishing off work to elucidate how TNFR1 signalling activates Bim as this mechanism has no precedent."