Distinguished Professor Antoine van Oijen has always had a desire to understand how things work. As a child, he was constantly getting into trouble with his parents for dismantling everything he could get his hands on to see its inner workings. These days are no different, although he has taken this fascination to a whole new (molecular) level.
I n the 1950s the work of James Watson, Francis Crick, Rosalind Franklin and Maurice Wilkins led to the discovery of the double helix structure of DNA. This twisted ladder of genetic code has been labelled as one of the most important scientific discoveries of all time and led to the modern era of molecular biology.
This structure is important because it provides a very accurate template for duplication – a blueprint for life.
Each rung of the ladder is a fixed pair of DNA bases – adenine always pairs with thymine and cytosine always pairs with guanine. To duplicate a cell, a protein splits the ladder in two and separates the bases. These two strands can create a new ladder using the missing base pair. This process is highly accurate with only one mistake in every one billion pairs.
“We have 100 trillion cells in our body,” Professor van Oijen says. “Knowing that each cell divides on average 50 times in our life and has to copy 6 billion DNA bases for every division, it’s amazing that the majority of us don’t get cancer from mistakes in this process.”
Seeing what’s happening during these duplications could lead to major scientific breakthroughs. Professor van Oijen likens it to drone footage of a marathon: you can see a swarm of people moving, but you need to see the actions of each individual runner to get a better understanding of the race.
“Visualisation is a strong enabler for scientific discovery,” he says.
A new horizon
Professor van Oijen trained as a physicist in the Netherlands, before a growing fascination for biology saw him move to the USA and establish a research group at Harvard Medical School. Later, he returned to the Netherlands as a professor at Groningen University where he focused on single-molecule visualisation. In 2015 he moved to UOW and was awarded a prestigious Laureate Fellowship by the Australian Research Council.
He is now the director of Molecular Horizons – UOW’s world-leading molecular and life sciences research facility which is currently under construction. Housing 150 researchers, Molecular Horizons will be dedicated to understanding how life works at a molecular level to solve some of the world’s biggest health challenges.
“It’s an initiative of the University that will put scientists from physics, chemistry and biology together and have them study how proteins work inside our cells and how they are involved in disease,” Professor van Oijen says. “DNA replication proteins are involved in a large number of disease pathways and represent important drug targets.”
Going in for a closer look
To help visualise these molecular interactions, UOW has invested in Australia’s most advanced and powerful microscope, capable of visualising down to the level of individual atoms.
At three-metre tall and weighing more than one tonne, the FEI ThermoFisher Titan Krios cryo-electro microscope uses electrons rather than light to look at molecules. It fires a stream of high-energy electrons through a frozen sample to generate multiple two-dimensional images that scientists then convert to three-dimensional models of molecules, visualising their nano-sized loops and chains.
“It’s like something straight out of a science fiction movie,” Professor van Oijen says. “The molecular details it reveals are so small and precise it allows us to map out every nook and cranny of the surface of biological molecules, such as proteins and DNA.”
UOW has also acquired a second microscope, the Talos Arctica, which is a smaller version of the same sophisticated imaging technology and complements the flagship Titan Krios with faster sample preparation.
A molecular magnet for researchers
The best research isn’t done in isolation and Professor van Oijen has no intention of locking this technology away for the sole use of UOW researchers. He believes if we are to make advances in the field molecular biology, it’s important that the world’s brightest minds – along with early career researchers and students – have access to the world’s best technology.
“I think it will draw in a lot of researchers from all over the country and overseas,” Professor van Oijen says. “It will allow us to establish more scientific collaborations.”
These collaborations have started even before the Titan Krios microscope is placed in its purpose-designed Molecular Horizons building on UOW’s Wollongong campus.
“UOW and ANSTO have come together to make available a facility to house the Titan Krios while its future home is built,” Professor van Oijen says. “Thanks to the partnership between UOW and ANSTO, the Titan Krios will become operational and accessible to researchers almost two years before its final home is completed.”
Getting to know the enemy
“One of the major challenges in the molecular life sciences is to understand the individual molecules and proteins involved in a disease,” Professor van Oijen says.
“Medical research has come a long way in understanding disease and finding cures. But most of the drugs we prescribe – in most cases very successfully – have been discovered basically by trial and error.
“Seeing and understanding what’s happening at the molecular level will help scientists discover cures for diseases such as motor neurone disease, Alzheimer’s and cancer, as well as tackling health challenges like antimicrobial resistance.
“Seeing is believing,” Professor van Oijen says. “Visualising how proteins look like and how drug molecules might interact with them is a critical step – it’s almost like knowing exactly how the inside of a lock looks like so you can design the key instead of having to pick the lock with a paperclip.”
“Working in combination with the other technologies at Molecular Horizons it will unlock the door to an unprecedented understanding of how life works.”
Animation by Jasper Smith