Cell Signalling and Cell Death

Cell Signalling and Cell Death

JAK2 bound to a blocking compound
The Cell Signalling and Cell Death division investigates the molecular mechanisms by which cells kill themselves, and the control processes that switch cell death on and off.
Many diseases are characterised by too much or too little cell death, and understanding how this process happens will help us develop new treatments for cancers and immune disorders.

Treating stomach and bowel cancers

Bowel and stomach cancers are two of the most common cancers.

When a tumour develops, normal tissues around it can become inflamed, producing signaling molecules (cytokines) that promote the growth and spread of cancer cells.

Associate Professor Matthias Ernst, Dr Tracy Putoczki and colleagues found interleukin-11 (IL-11), a potent cytokine, was an important stimulator of cancer growth and spread of bowel and stomach cancers. Working with scientists at CSL, they showed blocking IL-11 stopped tumour growth and could lead to tumour shrinkage, making IL-11 a promising new target for treating solid cancers.

Overturning a cell death myth

Programmed cell death, or apoptosis, is a natural process used by damaged or diseased cells to destroy themselves without damaging other tissues in the body.

Dr Lisa Lindqvist and colleagues are studying the relationship between cell death and autophagy. Autophagy is when cells eat themselves, a process cells use to recycle their components. It was believed Bcl-2 and similar ‘pro-survival’ proteins controlled autophagy, as well as apoptosis. However Dr Lindqvist research overturned that theory, showing the ‘pro-survival’ Bcl-2 family proteins only inhibited autophagy indirectly, by acting on other apoptotic molecules.

This was an important finding, because clinical trials had been planned based on the earlier, flawed model.

New anti-inflammatory drug target

Institute scientists have revealed the three-dimensional structure of a protein essential for triggering a recently discovered cell death mechanism called necroptosis.

They have used genetics to show that the protein MLKL is essential for triggering necroptosis. The structure revealed that although MLKL is a ‘dead enzyme’, it still needs to be switched on before necroptosis will occur.

The team is now trying to determine the ‘on’ and ‘off’ states of MLKL, making possible the development of new drugs that may help treat chronic inflammatory diseases such as inflammatory bowel disease, psoriasis and rheumatoid arthritis.

Health impact

Cancers: bowel cancer, breast cancer, lung cancer, leukaemia, lymphoma, myeloproliferative disorders, stomach cancer

Immune disorders: inflammatory bowel disease, psoriasis, rheumatoid arthritis

Lab heads

Professor David Vaux, Joint Division Head

Associate Professor John Silke, Joint Division Head

Dr Grant Dewson

Dr James Murphy

Scientific coordinator

Catherine McLean

Michelle Birrell, Administrative Officer