Structural biology of proteins involved in cancer

Summary We are investigating, though structural and biochemical means, how a range of ruthenium, arsenic and osmium-based drugs and drug-like compounds interact with Glutathione S-Transferase (GST) family of proteins.

Project Details

Conventional cancer chemotherapy kills rapidly growing cells indiscriminately, causing significant side-effects and can lead to disease re-occurrence and resistance to the drugs. One of our interests is the Glutathione S-Transferase (GST) family of proteins that function by recognising foreign small molecule toxins in the body, causing them to be eliminated from the cell. Unfortunately, commonly used anti-cancer drugs are also recognised as toxic by GST, which is often overexpressed in cancer tissues and is associated with transformation to malignancy and the adaptive resistance to anti-cancer drugs. There is thus an urgent need for the design of new anti-cancer drugs that circumvent the development of GST-mediated resistance to treatment. Very recently, there has been an increasing interest in the development of metal-based drugs as effective and potent protein targeted chemotherapies. We are investigating, though structural and biochemical means, how a range of ruthenium, arsenic and osmium-based drugs and drug-like compounds interact with GSTs. Students will investigate how these compounds work, as well as any drug-like molecules we develop, using X-ray crystallography and a range of biophysical techniques.

This project is conducted in St Vincent’s Institute of Medical Research, Structural Biology Unit.