Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please could you give a brief introduction to the Children’s Medical Research Institute’s (CMRI) discovery program?
The reason Children’s Medical Research Institute (CMRI) exists is to find ways to treat or prevent childhood disease. Our research programs are focussed on the areas of cancer cell growth, nerve cell signalling, embryology and gene therapy. These four programs have a shared aim of translating novel findings into new treatments for the benefit of families everywhere.
We are developing new medicines to treat cancer, epilepsy, kidney disease and infectious disease. Our Gene Therapy Unit, a collaboration with the neighbouring Children’s Hospital at Westmead, conducted the first ever gene therapy clinical trial in Australia, and they are continuing to make improvements in gene therapy technology. They now have two gene therapy clinical trials ongoing, one to help children with inherited liver disease and one to improve chemotherapy treatment for brain tumours.
We are currently working towards a building expansion that will increase our number of researchers and our research output, as well as provide much needed space for the national research facilities that we operate for the benefit of researchers throughout Australia: CellBank Australia and The ACRF Centre for Kinomics.
You have recently received a grant from the Ramaciotti Foundations to purchase a Typhoon FLA9500 Biomolecular Imager. What can this biomolecular imager be used to visualise?
The imager can help visualise DNA, RNA and protein, the latter being crucial to proteomics work.
How will this piece of equipment aid the expansion of CMRI’s discovery program?
The imager, which Ramaciotti Foundations have kindly helped support, is used by all of our research groups, and is especially useful for studying telomerase, one of the key factors in 85% of all cancers.
This new imager is essential, however, to increase the throughput of our mass spectrometry work.
CMRI houses a Biomedical Proteomics facility that collaborates with researchers across New South Wales, and it also operates The ACRF Centre for Kinomics, a unique national resource that is available to researchers across Australia to aid the development of therapeutic drugs for a range of diseases including epilepsy, asthma, heart disease, infectious diseases and cancer.
All of this work requires expensive mass spectrometry equipment and the know-how to run it, but processing the samples prior to mass spectrometry requires a biomolecular imager. This new machine will play a vital role in allowing us to take full advantage of our proteomics facilities.
Please could explain what telomerase is? Why is it one of the key factors in 85% of cancers?
The DNA inside every cell of our bodies is packaged into chromosomes. The ends of chromosomes are called telomeres and they have a specialised structure that helps to protect chromosomes from being damaged. But each time a cell reproduces itself, its telomeres wear down a little bit. This acts as a counting mechanism determining the maximum number of times a cell can divide and may be one of the causes of aging.
Cancer cells, however, are able to ignore this countdown clock and keep growing indefinitely. The way they do this is by adding back new telomere DNA to the ends of chromosomes to prevent them wearing down. 85% of all cancers use an enzyme called telomerase to add back this telomere DNA. If we can find a way to block the action of telomerase in cancer cells, we can stop them from growing.
What further study is needed into telomerase and how exactly will this new imager help to achieve this?
CMRI'S Cell Biology Unit is studying the telomerase protein in great detail to understand how every part of it works. One of the approaches they take is to remove the function of small parts of the enzyme to see what effect this has, which allows them to build up a picture of how all the parts of the enzyme work together.
This approach requires them to measure how well telomerase works after they have made these alterations. These measurements require a Typhoon imager in order to visualise the DNA telomerase is adding on to telomeres. The Cell Biology Unit also needs the Typhoon to help study the telomerase protein itself. They expect that their work will reveal the best target areas within telomerase to aim for when designing new anti-cancer drugs.
Why is it necessary to use a biomolecular imager to process samples prior to mass spectrometry?
Proteins for mass spectrometry study usually come from complex mixtures and first need to be separated from one another by methods such as a polyacrylamide gel. This is a jelly-like material to which an electric field is applied to separate proteins from one another based on their size and electric charge. Then, in order to visualise the proteins, the Typhoon imager is needed.
Next, they are prepared for mass spectrometry analysis. Mass spectrometry analysis requires extensive preparation of samples ahead of time and purification of those samples using either gels (requiring a Typhoon) or HPLC (another instrument that helps separate proteins). The method used depends on the type of analysis that the researchers require.
How does the new biomolecular imager differ from current instruments owned by the CMRI?
It detects a greater range of wavelengths, is more reliable and has higher throughput capabilities.
Why does the new imager have higher throughput capabilities?
The instrument we’ve chosen can hold more polyacrylamide gels at once than other imagers that are currently available —thus increasing throughput.
What research benefits do you hope will come from this Biomolecular Imager?
We hope the new imager will seamlessly integrate with our current research programs and also provide the capacity for expansion as CMRI grows over the next few years.
It will have a role to play in diverse areas of research ranging from a detailed understanding of the role of the telomerase enzyme in cancer, to helping to identify other proteins involved in cancer, neurological conditions including epilepsy, and a variety of other diseases.
Would you like to make any further comments?
As ever, we are extremely grateful for Ramaciotti Foundations’ support of our work. The Ramaciotti Foundations are a vital source of funding for the specialised equipment that our research depends on.
Where can readers find more information?
For further information on the Children’s Medical Research Institute (CMRI): www.cmri.org.au
For further information on the Ramaciotti Awards: http://www.perpetual.com.au/ramaciotti/
About Professor Roger Reddel
Roger Reddel is Director of Children's Medical Research Institute (CMRI), and the Sir Lorimer Dods Professor, Sydney Medical School, University of Sydney. He also heads CMRI's Cancer Research Unit, and directs CellBank™ Australia.
He obtained his medical degrees from the University of Sydney, trained in medical oncology at Royal Prince Alfred Hospital, and is a Fellow of the Royal Australasian College of Physicians.
Roger completed a PhD in cancer cell biology at the Ludwig Institute for Cancer Research in the University of Sydney's Department of Cancer Medicine, and received an NHMRC CJ Martin Fellowship and a Fulbright Fellowship to undertake postdoctoral research at the National Cancer Institute, Bethesda, Maryland, USA.
He returned to Sydney to establish a laboratory at CMRI, attracted by the Institute's culture of fostering high quality basic research, and with the support of Cancer Council NSW's Bicentennial Fellowship.
He has continued to receive major support from the Cancer Council, including being awarded the Carcinogenesis Fellowship for ten years, and Program Grants for ten years. His team is also supported by Cancer Institute NSW, the Judith Hyam Memorial Trust Fund for Cancer Research, Rotary Club of Sydney, and the National Health and Medical Research Council of Australia.
Professor Reddel was awarded the Ramaciotti Medal for Excellence in Biomedical Research in 2007, was elected as a Fellow of the Australian Academy of Science in 2010, and in 2011 received the NSW Premier's Award for Outstanding Cancer Researcher of the Year.
Professor Reddel is a director of Cure Cancer Australia Foundation. He serves on editorial boards of a number of international cancer research journals, and on national and international scientific advisory panels.