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A joint discovery by Australian and German scientists opens up new possibilities for the development of novel therapeutic approaches for the treatment of cancer, viral or bacterial infections and neurological disorders.
Scientific research by the Children’s Medical Research Institute (CMRI), The University of Newcastle (UoN) and University of Berlin, for the first time has identified small molecules that inhibit clathrin, a protein that performs a critical function called endocytosis in all cells in the body. These new small molecule compounds named ‘Pitstops’ are able to prevent the uptake of signalling molecules which stimulate cell growth and division, or the entry of viruses such as the human immunodeficiency virus (HIV) or some bacteria into human cells.
“Our study focused on clathrin-mediated endocytosis which is the main route for endocytosis in cells throughout the body. By enhancing our knowledge of the role of proteins in endocytosis, including clathrin, we can ultimately attempt to prevent the spread of some diseases in the body,” explained Professor Phil Robinson, Head of the Cell Signalling Research Unit, Children’s Medical Research Institute.
The development of Pitstops opens up the possibility of designing much more effective treatments for cancer such as brain tumours whose growth depends on the uptake of signalling molecules, which control cell division. Furthermore, Pitstops, and like substances, could open new avenues for the treatment of serious neurological disorders such as epilepsy.
“We have identified new compounds that offer a starting point for the development of novel therapeutics approaches for serious diseases that currently have no cure. This opens up the possibility of designing much more effective, targeted treatments for diseases such cancer,” said Professor Robinson.
To identify the Pitstop compounds that specifically inhibit binding of clathrin to its partner proteins, the researchers tested a library of approximately 20,000 different small molecule compounds and followed this with medicinal chemistry-based synthesis of even more compounds.
The study, led by Professor Volker Haucke, was a multinational collaboration involving researchers at the University of Berlin, Children’s Medical Research Institute in Sydney and University of Newcastle. The new findings are published online (5 August) in the prestigious international journal CELL.
Sir Lorimer Dods Professor Roger Reddel, Director of Children’s Medical Research Institute, welcomed the results of the new study and highlighted that the findings were the result of a successful multinational collaboration.
“Professor Robinson and his team have made major contributions to understanding key aspects of nerve cell communication, principally the process of endocytosis and the protein dynamin. This new finding builds on our current knowledge and is particularly important for future research into the prevention of viral diseases such as HIV.”
“This research, which has been conducted in close collaboration with our partners in Newcastle and in Germany, is an outstanding example of what can be achieved by scientists using their skills cooperatively across different disciplines,” said Professor Reddel.
The work carried out by Professor Robinson and his team at CMRI was partly funded by Jeans for Genes, the major national fundraiser of the Institute. Australians can support the ongoing work of the scientists at CMRI by wearing jeans and buying a badge or making a donation, or taking part in events including Jump for Genes throughout August.
Making the fundamental discoveries that lead to major advances for the treatment of cancer and other serious diseases requires significant investment. Without the community support of Jeans for Genes, scientists at CMRI would not be able to continue their important work today for the medical advances of tomorrow.
“We have world-class research programs at CMRI in each of our four key research areas: cancer, embryology, gene therapy and neuroscience. Our research helps us understand normal development and health, and what goes wrong in disease. Continuing our research work is dependent on the support of the community,” added Professor Reddel.
By getting involved in Jeans for Genes, supporters are helping scientists make the advances needed for future improvements in children’s health. Individuals and groups across Australia such as schools and businesses can take part in Jeans for Genes and help create healthier generations by donating or registering to hold a fundraising event at www.jeansforgenes.org.au
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