November 1, 2012  Print

A luncheon co-hosted by the Australian Friends of the Hebrew University and the Sir Zelman Cowen Universities Fund was the occasion for the presentation of the 2012 award of the Sir Zelman Cowen Universities Fund Prize For Discovery In Medical Research to Associate Professor Barry Slobedman, Sydney Medical School and Westmead Millennium Institute.

Professor Slobedman was nominated for the Prize for discoveries which have profoundly changed our understanding of how the human cytomegalovirus (CMV) can persist in a dormant state for the life of the human host, despite the presence of a huge anti-viral immune response.

The discovery provides a novel drug target for development of therapies to interrupt the dormant state of infection, and so limit or prevent the devastating consequences of reactivation from dormancy in immunocompromised individuals such as transplant patients.

It may also lead to development of a live CMV vaccine. Its potential for clinical applications has led to an international patent sponsored by Sydnovate, the commercial arm of the University of Sydney.

Speaking at the function, Professor Slobedman explained that the true significance of his work lay not just in its value to the immunocompromised individuals, in whom this virus might come out of its dormant state to cause harm, but also to new born babies and young children.

Despite being rarely heard of, he explained, "This virus is the number one infectious disease that occurs in the developing fetus during pregnancy, often with devastating consequences. The really nasty aspect to this infection is that the pregnant women usually have no symptoms of
infection, and so are oblivious to the damage being caused by this virus to their developing fetus.

"This infection often leads to interuterine death (stillbirth), or birth of babies with profound neurological defects, such as mental retardation and hearing loss. In fact, CMV causes more serious disease than Down Syndrome, neural tube defects such as spinal bifida, and fetal alcohol syndrome. Yet only a small minority of pregnant women (and others in the
community) have ever heard of CMV." 

Moreover he said, “CMV infection does not only occur in pregnant women and transplant recipients. Rather, most of the world’s population is actually infected with this virus.

"For example, if I took some blood from everyone in this room, I can say with some certainty that about 70% of the people in this room would currently be infected with CMV.”

“You may have caught this virus as a toddler or in your early adult years, but you probably never had any symptoms of infection. This is because your body mounted a huge immune response to control the virus before it could cause disease.

"The problem is that, whilst your immune system largely prevented you from experiencing symptoms of disease, it was never able to completely eliminate the virus from your body. Instead, this virus has very cleverly worked out a way to hide in your body, for the rest of your life, by converting itself into a dormant state called latency, where it waits for an opportunity to reawaken and cause disease.

"So, even though a massive proportion of your immune cells become specifically programmed to detect and kill only CMV infected cells, these “soldiers” of your immune system are never able to recognize and eliminate the dormant virus from your body.

This, as my team discovered, is because even when this virus is in its dormant form, it remains active, and makes a protein which renders infected cells invisible to the CMV-specific immune soldiers.

"Thus, even though our immune soldiers are fully functional, with their “gun-sights” aimed at CMV, they simply can’t see which cells contain CMV, and so pass by infected cells, without realizing that they are the cells which should be destroyed.”

In conclusion, Professor Slobedman said, “This work has now also led to a whole new area of research at an international level into understanding how CMV controls the immune system, even when the virus is in its dormant form, as this was a previously unrecognised phenomenon.

We continue to work hard at defining the key parts of CMV that should be targeted with anti-viral drugs and will also need to be considered in developing a vaccine against CMV.”

On receiving the Prize, Professor Slobedman also acknowledged and thanked the many members of his team for their contributions to his work. He gave particular thanks to Professors Tony Cunningham, Warwick Britton and Craig Mellis for their mentorship and support and special thanks to his nominator, Professor Allison Abendroth.

The Prize, an award of $10,000 and a medal crafted by renowned Melbourne sculptor, Michael Meszaros, was presented to Professor Slobedman by Wendy Morel of The Schwartz Foundation, sponsors of the 2012 award of the Prize.

The Prize is presented in alternate years at the University of Sydney and at the Hebrew University of Jerusalem. It is just one of a number of initiatives of the Sir Zelman Cowen Universities Fund supporting medical research and promoting co-operative work between the two Universities.

Professor Shy Arkin, Head of the Authority for Research and Development at the Hebrew University, and the Deputy Vice-Chancellor (Research) of the University of Sydney, Professor Jill Trewhella, both attended the function and spoke about recent highlights in medical and scientific research at their universities, as well as providing their own perspectives on co-operative research between universities.

Professor Arkin emphasised the enormous benefits researchers and universities were able to gain from strategic alliances between research groups at various universities which allowed a reduction in costs and quicker outcomes as ideas and resources were shared rather than repetitively re-invented for sole use.

Through such alliances he said, it became possible for 2 plus 2 to become greater than 5. He said that, as Head of the Authority for Research and Development at the Hebrew University, he felt that one of the most important aspects of his role was not to interfere. It was particularly pleasing to have seen many projects flourish, including those between scientists of HU
and Sydney University such as the collaborations supported by the Fund’s Blue Sky Research Grant Program between Professors Yehudit Bergman (HU) and Jacob George (USYD).

Professor Trewhella highlighted a number of ground breaking projects currently underway at the University of Sydney, which are coincidently being carried out by scientists who have received support from the Fund to assist them in, for instance, making the trips between universities sometimes needed to set-up and or progress collaborative projects.

“One of those researchers” she said “is Professor Tony Weiss, who is developing ways to use his understanding of the properties of human tropoelastin protein to synthesise biomaterials that can augment and repair human tissues.

"The latest discovery from his work is the development of sophisticated blends of tropoelastin and silk to make multifunctional materials that have been found to direct tissue growth. Professor Weiss, with colleagues from Engineering at Sydney University RPAH, collaborates with researchers all over the world; including Tufts University, MIT, and the Hebrew University of Jerusalem. He is currently developing scalable units of these biomaterials for building vascularised cardiac grafts that will enable us to replace damaged blood vessels, work that has direct relevance for treating cardiovascular diseases.”

She went on to trace a number of equally forward-looking examples of what may be possible in the not-too-distant future.

She said, “Breakthroughs in research most frequently come as a result of work at the interfaces of the disciplines, when methodology or capability from one discipline impacts other areas. Such breakthroughs often require state-ofthe-art research infrastructure which the Charles Perkins Centre will provide.

"Tropoelastin inspired biomaterials are one example of what is essentially “materials research” having an impact in medicine and beyond.”

Another example she gave was the work of Professor Nicholas King who is using nanotechnology as part of his research aimed at treatments for autoimmune diseases, particularly multiple sclerosis but also potentially type 1 diabetes and rheumatoid arthritis, as well as immune-mediated diseases, such as food allergy and asthma.

While current therapies work by suppressing the immune systems attack on it-self, a big advantage of Prof King’s new approach is that, “ It does not cause blanket immunosuppression, but only causes a specific tolerance to the myelin proteins that are key to the development of multiple sclerosis. This technique is much cheaper to produce, easier to standardise than other
techniques, and is based on a biodegradable nanoparticle already approved by the Federal Drug Administration.

Professor King collaborates with a group at Northwestern University in this work and also has collaborative links to the Hebrew University of Jerusalem supported by the Zelman Cowen Fund.

The presentations brought to life for the audience, the impact and value of the Fund’s support and vision in helping to make scientific breakthroughs into medical applications.

The Sir Zelman Cowen Universities Fund was established in 1978 by the late John Hammond, a Sydney  businessman, to raise funds for medical and scientific research and to lay the foundation for cooperative work between the University of Sydney and the Hebrew University of Jerusalem.

Currently, the Fund supports a number of scientific projects between the two Universities, a program of student and academic exchange, the Fund Prize for Medical Research, the SZCUF Alzheimer's Disease Research Grant and most recently, the Blue Sky Research Grant Program.