Burnet Prize awarded for cell signalling discoveries
The proteins, called suppressors of cytokine signalling (SOCS) proteins, are important for blood system maintenance and regulating the immune response. They could also play a role in treating conditions such as leukaemia and arthritis.
Dr Babon said he was incredibly humbled to win the Burnet Prize. “It is an honour to win this award, both because it was named after such a great Australian scientist and because of the amazing people who have won the award before,” he said. “Two previous Burnet Prize winners, Robyn Starr and Doug Hilton, discovered SOCS proteins, so my work is built on theirs. I’ve always felt privileged to be a scientist; it is the most amazing career in the world. I don’t know anyone outside science who looks forward to going into work every day the way that we do.”
Dr Babon has spent more than nine years at the institute studying SOCS proteins. “SOCS proteins were discovered at the institute in the 1990s, and provide a necessary ‘negative feedback’ response to control the blood and immune systems,” Dr Babon said. “We are trying to understand how the body naturally regulates cell signalling using SOCS proteins, to give us clues about how to enhance or dampen the response in cases where it has gone awry and caused disease.”
Some types of leukaemias and, in particular, myeloproliferative disorders (MPDs) are caused by over-active signalling in blood cells. Myeloproliferative disorders, such as polycythemia vera and myelofibrosis, are serious blood disorders in which an excessive number of blood cells accumulate in the bone marrow, which can lead to bone marrow failure.
Dr Babon said new drugs could be made that treat these diseases by developing a better understanding of how the body controls and maintains the blood and immune systems. In 2011, Dr Babon and Professor Nick Nicola made an important discovery about how SOCS proteins (in particular SOCS3) bind to a molecule called JAK2 (janus kinase-2). In the future, this discovery could lead to new treatments for leukaemias and MPDs, as well as inflammatory diseases such as arthritis.
“Almost all of the proteins and enzymes in our body have a very particular and exact molecular shape,” Dr Babon said. “The way that we go about developing drugs that target particular proteins or enzymes is to determine their three-dimensional shape and use this shape to identify ‘pockets’ that are critical to the protein’s activity. Most drugs are small molecules that sit in that specific pocket to prevent the protein from functioning correctly.
“Drugs that target JAK2 do exist, but they are not specific enough and cause significant side-effects that make them undesirable for use in humans. We decided to let nature show us how JAK2 and SOCS3 interact in order to learn how SOCS3 normally halts JAK2 activity. When we solved the structure, we were surprised to find that SOCS3 binds to a part of the JAK2 protein that is not targeted by current therapies. We are now looking to develop drugs that exploit this new site as a drug target, and we think the drugs will be much more specific, and hence more attractive as a human drug, than any other currently in clinical trials for inhibiting JAK2.”
Institute director Professor Doug Hilton said Dr Babon was a worthy winner of the Burnet Prize, which recognises scientists who are in the prime of their careers. “Jeff is at the top of his game from a research viewpoint,” Professor Hilton said. “He is willing to tackle difficult problems and, in doing so, creates really beautiful science. We are very proud to have him at the institute.”
The Burnet Prize is awarded annually to early-career scientists at the Walter and Eliza Hall Institute who have produced pioneering research. It was established in 1987 through a bequest of Sir Macfarlane Burnet and includes a cash prize of $2000 and a bronze plaque created by Melbourne sculptor Michael Meszaros.
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