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Scientists in Australia have unravelled the structure of a cell signalling receptor in the blood control system which when damaged is responsible for diseases such as leukaemia. Their discovery helps to explain, for the first time, how this receptor is activated and will form the springboard for the development of new treatments.
The findings, published on 8 August in the prestigious science journal, Cell, are the result of an interstate collaboration between a team of scientists led by Professor Michael Parker from St Vincent’s Institute (SVI) Melbourne and Professor Angel Lopez from the Hanson Institute at the Institute of Medical and Veterinary Science in Adelaide.
Using leading edge technology that allows scientists to view minute parts of cells, the scientists have developed the first 3D image of the receptor’s structure and will use the unique knowledge it provides to find drugs to modify its action and control diseases such as Leukaemia and asthma.
Professor Lopez said, “Leukaemia is a type of cancer where an excessive number of malfunctioning white blood cells are produced. We have established the structure of a receptor that controls the actions of a blood-forming regulator called GM-CSF.”
“GM-CSF has been of interest to researchers and clinicians for many years now because its ‘controller’ or ‘receptor’, found on the surface of blood cells, is critical in regulating their many functions. In leukaemia some of the signals coming from the “receptor” are abnormal causing the blood cells to grow uncontrollably, malfunction or dangerously persist past their use-by-date.”
Michael Parker is an Australian Research Council Federation Fellow and a National Health and Medical Research Council Honorary Fellow. “Because our discovery shows precisely what the receptor looks like and also how it works, we can now begin to design new drugs to rein in the deadly abnormal blood cells. At the moment many leukaemias are treated with chemotherapy that destroys the diseased blood cells and bone marrow as well as normal cells. We hope that this discovery will lead to targeted therapies, more specific to the malfunctioning cells seen in diseases such as leukaemia,” Professor Parker said.
“To maximise the drug development opportunities of this discovery both Institutes have recently signed an agreement with biopharmaceutical company CSL Limited. Under the agreement the Institutes will work with CSL to discover and develop new therapeutic antibodies.”
Co-first authors of the Cell report are Dr Guido Hansen from SVI and Dr Tim Hercus from the Hanson
Institute. The study was supported by grants from: Australian Research Council, Australian Synchrotron Research Program, National Health and Medical Research Council of Australia and National Institutes of Health (U.S.).