Shining a light on brain cancer

PhD student helping to treat insidious disease

Elette Engels, winner of the Australian Institute of Physics Postgraduate Excellence Medal, is part of a team of scientists searching for a better way to treat brain tumours.

It's 1.30am at the Australian Synchrotron in suburban Melbourne and Dr Moeava Tehei is singing along as AC/DC's TNT blares out from his mobile phone.

The University of Wollongong (UOW) physicist has been awake for 18 hours. "I'm tired but the data we're getting is interesting so sleep can wait," he says, looking up from a fluorescence microscope, cell counter in hand.

"For the week after, you feel jet-lagged," says Dr Tehei. "It doesn't get any easier. But it's always exciting to come here and use this amazing machine."

Downstairs at the Imaging and Medical Beamline, Professor Michael Lerch, head of UOW's School of Physics, is working with a team of UOW PhD research students, sorting through experiment samples. "I'll stay up until 8am and then be back here by midday. It's going to be a busy few days," he says.

On a nearby desk lies a pile of sugary snacks, potato chips and chocolate bars, along with empty Coca-Cola cans and coffee cups; the dietary requirements of the scientists as they work round-the-clock.

Housed in a circular building the size and shape of a cricket ground, the Australian Synchrotron works 24-hours a day pulsing out high-energy X-ray beams that it makes by spinning electrons around in a circular pattern at close to the speed of light (about 299,792 kilometres per second).

As they spin around a large central ring the electrons produce light a million times brighter than sunlight. This light is spat out as X-rays and channeled down evacuated pipes along the beamlines to experimental workstations, where researchers use it to study the molecular structure and composition of materials ranging from human tissue to plants to metals and more.

The team from UOW's Centre for Medical Radiation Physics (CMRP) is using these X-rays to explore a way to treat otherwise untreatable brain cancers using image-guided microbeam radiation therapy (MRT), part of an ongoing 15-year research program. They have only a few precious days at the Synchrotron to conduct experiments and collect data crucial for their research. "Our time at the Synchrotron is precious. It will be months before our next visit," Professor Lerch says.


The battle against brain cancer

Among the PhD students is Elette Engels, who was recently awarded the Postgraduate Excellence Medal by the Australian Institute of Physics, becoming the first UOW student to win the prestigious honour. She says brain tumours are among the most difficult cancers to diagnose and treat. Often they're not detected until they are quite advanced, and whatever stage they are diagnosed at, removing them is problematic.

"Brain tumours are horrible," Elette says. "They are so difficult to treat, especially in children. They can be impossible to remove surgically and there are risks for normal tissue around them. On top of that, they can be very resistant to radiation and drug treatments as well."

MRT uses ultra-fine X-rays - each smaller in diameter than a human hair - which can be directed more accurately, destroying the cancerous tissue while not harming the surrounding healthy tissue. This precise targetting also means much higher dosages can be delivered to the tumour.

"This new MRT technique treats tumours with very narrow wafer-like X-ray blades to deliver very high doses of synchrotron radiation delivered in a very short time," Elette says. "This is not feasible with conventional radiotherapy X-ray machines in hospitals. My research shows that the treatment of tumour cells is much more effective when the radiation dose is delivered using MRT."

Elette is also looking at whether certain nanoparticles can enhance the effectiveness of MRT, both in mapping the tumour and in increasing the radiation damage to the tumour.

"I'm looking at nanoparticles that could be used for image-guided radiotherapy and trying to find a better way to attack brain tumours that are resistant to radiation," she says.

"This involves growing tumour cells in the lab and learning how they behave when treated with radiation. Then we introduce nanoparticles to find out if that increases the damage you can deliver to the tumour.

"We want to reduce the radiation dose to the brain, while ensuring the tumour gets treated effectively. I found that with nanoparticles we can do both: get more targeted damage to brain tumours and potentially lower the radiation dose given, which is a start towards better treatment."

What's more, she adds, certain types of nanoparticles make it easier to locate the tumour, using MRI (Magnetic Resonance Imaging) or CT (computed tomography scans), before and during treatment.


 The Australian Synchrotron is the home of accelerator physics research in Australia. Photo: Paul Jones

From theory to practice

With time at the Synchrotron at a premium, hours and hours of preparation is required in order to understand the physics involved before any experiments are run.

"It's so much more complicated than just adding nanoparticles to tumour cells and seeing what happens," Elette says. "You really have to look at it from a physics point of view: how does radiation interact with the nanoparticle? What factors do you need to consider for imaging or treatment? How does it affect the cell from a biological and chemical standpoint?

"At the beginning, a lot of my research was about trying to understand it at a theoretical level, and then apply what we found to real cells and seeing whether it works in practise - and I've been able to prove that it does work really well for conventional radiation treatments and MRT.

"We'll be the first in Australia to do a long-term study on using MRT guided and enhanced with nanoparticles to treat brain cancer at the Australian Synchrotron, so it's pretty exciting and hopefully will yield some really good results."

While Elette enjoys the intellectual challenge of the science, the fact her research might one day save lives gives her additional motivation.

"It's something I'm passionate about. Having that passion drives me to want the research to work to provide an answer for those suffering from these kinds of cancer."


 "My research shows that the treatment of tumour cells is much more effective when the radiation dose is delivered using MRT." - Elette Engels

From farm to physics lab

Two years into her PhD, Elette is amazed by how far she has come since finishing high school. "It's pretty scary actually, to think I'm working with experts in physics while growing tumours in the lab! And it's really just a few years after coming out of high school," she says.

Even more so when she remembers the struggles she had trying to decide what to study at university. Like many others, Elette was caught in two minds: in her case the question was whether to follow her love of maths, or to pursue her lifelong ambition of a career in medicine.

"I'd always planned to do medicine, but I love maths and technical sciences and thought I'd miss that side," she says. "At school I did all the sciences I could - chemistry, biology, physics. My whole family are engineers so I've got that kind of technical background."

Elette's dilemma was resolved when she learnt about UOW's medical radiation physics degree, which combines hard science with a strong medical focus. "It was perfect for me, lots of maths and science but then you use theoretical and practical physics in medical applications."

Born in the Netherlands, Elette's family migrated to Australia when she was five, settling on a rural property near Nowra. While her research frequently takes her to Sydney and Melbourne, she admits she prefers the country lifestyle.

"We lived on a farm down a dirt road. It's really quiet out there. It's peaceful. I used to commute up to university on the train and it would often be delayed because of cows crossing the tracks!" she says.

"Wollongong was a bit too fast paced for my liking and then going up to Sydney to do experiments at Prince of Wales Hospital was worse. Whenever I have to drive up to the city I'm thinking, these people are crazy!"

A nice way of understanding the world

While the AIP Medal marks her out as one of Australia's top postgraduate physics students, Elette says physics was something she had to work hard at.

"It was hard at first because I felt I wasn't naturally gifted with physics, but I soon began to appreciate that it's a really nice way of understanding the world. Physics gives you an explanation, a theory behind how things work," she says.

"And then to go and apply that to the human body, to look at MRI and CT imaging and to work towards better cancer diagnostics and treatments - it's fascinating." Because of the nature of her work, Elette has also had to study up on chemistry and biology.

"It's been a good journey, to start from theory in physics and then explore the realms of biology and chemistry. I've had to catch-up and learn really quickly," she says.

While physics is sometimes seen as male dominated, Elette has never viewed it that way. Given her family's background in science and engineering it felt natural to pursue a career in the sciences.

"I've certainly not found physics to be male dominated," she says. "There's so many of us women in the School of Physics doing PhD research and we have just as much ability as anyone. Even at the AIP Awards, I definitely wasn't the only girl there either.

"It's a great field for women to get into if they're interested in maths and in medical applications as well."


 "We want to reduce the radiation dose to the brain, while ensuring the tumour gets treated effectively." - Elette Engels.

A multidisciplinary team

The multidisciplinary nature of her PhD research has meant Elette has needed to draw on the specialised knowledge of a large group of co-supervisors and mentors. "One of the really great things about studying here at Wollongong is that you get to meet experts from all backgrounds and so many different fields of research," she says.

"It started as a research project in third year of my bachelor degree using simulations to model how nanoparticles could improve radiation treatment. I was introduced to Dr Susanna Guatelli, Dr Moeava Tehei and Professor Michael Lerch from the Targeted Nano-Therapies Theme of the CMRP. I really liked the group, there is a lot of history and expertise, but the research was fast-paced and exciting.

"Then I had the opportunity to see nanoparticles in real cells, study chemical and biological aspects of this research at the Illawarra Health and Medical Research Institute (IHMRI). I've also performed real treatments on tumour cells at the Prince of Wales Hospital in Randwick with another of my supervisors, Dr. Stéphanie Corde, who's offered a lot of advice and guidance along the way."

Other supervisors and mentors include CMRP Director Distinguished Professor Anatoly Rozenfeld, and Associate Professor Konstantin Konstantinov from UOW's Institute for Superconducting and Electronic Materials.


 "I've definitely caught the research bug, so I'll be inclined to continue doing research." - Elette Engels

Elette believes the multidisciplinary nature of her research was one reason the judges selected her for the AIP Medal. Another was the practical applications of her work. "It was a great honour to be there with other physicists from six universities in NSW, all in their early careers. There were some very clever people there and I certainly didn't expect to win."

"After I got up and spoke they said, 'We can see you are headed towards a real goal: towards clinical studies where we can see your research applied.' That's why medical radiation physics is special: there's a clear pathway to applying the physics that you know, the theory that you know, to better medicine."

When Elette completes her PhD, she will have another decision to make: to continue in research or to work in a hospital. She hasn't yet decided which direction she'll take.

"I've definitely caught the research bug, so I'll be inclined to continue doing research," she says. "Research lets you get the most out of your potential, it's challenging and rewarding. You get to try things that no one else has done before. You can contribute to better the scientific community.

"With medical radiation physics, though, you have the potential to go into the hospital system and work directly with patients. It's a lot of responsibility and would be a good direction to go in too.

"In this field there's so much you can do, and maybe I can combine research with hospital work. I'll have to see where it all takes me."