In the competition to transform medicine with quantum technologies, Australia is off and racing. Still, it’s shaping up to be a marathon effort. Visit the cutting-edge Centre in Quantum Biotechnology, with quantum physicist Erin Grant. This article originally appeared in the Cosmos Print Magazine in December 2024.
In 5 universities across Australia, scientists are beginning some of the most exciting research of their careers. They will be using techniques underpinned by quantum mechanics to drive fundamental biological understanding and applications.
The collaboration is the Centre in Quantum Biotechnology, or QUBIC. It’s one of Australia’s Centres of Excellence, funded by the Australian Research Council.
QUBIC’s aims are diverse but its grand unifying goal is to transform our ability to understand biology and drive applications across research and industry within 3 main themes: molecules, cells, and brains.
The hope is that quantum technologies will offer more sensitive sensors and better simulations than classical technologies, with groundbreaking medical applications spanning drug design to epilepsy diagnosis.
The protein puzzle
Fundamentally, all biology results from interactions between molecules. Arguably, the most important of the molecules of life are proteins. Proteins not only make up the majority of our tissue, they also play a key role in controlling the chemical processes that occur in each living cell. Therefore, understanding the structure and function of individual proteins is one of the grand challenges of molecular biology.
If we can do this, we will not only build fundamental understanding but also open up opportunities for drug design and tackling diseases. One of the main targets for QUBIC researchers will be diseases like dementia, the leading cause of death of Australian women and second of Australian men. But unravelling the mysteries of the proteins involved in diseases like dementia is a difficult goal.
Proteins are made up of amino acids and the sequence of amino acids in each protein is stored in DNA. The sequence alone is not enough information to work out how a protein functions though.
“The different amino acids along the chain mean proteins adopt a wide variety of complex 3-dimensional folds,” Professor Alan Mark tells me. It’s the folding that determines a protein’s shape and how it behaves.
Mark is the leader of the molecules theme of QUBIC and heads a group at The University of Queensland (UQ). He has worked to simulate proteins and their interactions his whole career and knows exactly how challenging this can be.
One major difficulty comes from limitations in the experimental data used to inform these simulations. Ideally, the data would reflect the properties of a single protein, but standard experimental techniques measure a huge number of proteins over relatively long time scales to get sufficient signal.
This is a problem because proteins don’t stay still. Instead, each one is undergoing dynamic processes all the time. “Currently, measurements involve millions of molecules at once, with data averaged over tens of milliseconds or longer,” says Mark. That’s a long time when compared to the movements within proteins and it leads to uncertainty in the results.
Although Mark and his team do their best with this information, there are undoubtedly situations where crucial information has been missed.
The experimentalists in QUBIC hope to pick up the missing pieces by measuring single proteins over short timescales. “If we can truly get precise measurements from a single molecule, this dramatically changes how we can validate the models and know what we’re truly measuring,” says Mark.
Early career researcher, Dr Pavlina Naydenova, a postdoctoral scientist from UQ, will be performing some of these single protein measurements. In Naydenova’s experiments she first traps a protein with “optical forces”, sort of like a tractor beam in sci-fi. She then observes how the protein interacts with the optical field and is working towards being able to actively manipulate its dynamics.
This technique provides highly time-resolved information about a single protein. “A lot of enzymes work and move and their dynamics happen on nanosecond, or maybe microsecond timescales,” Naydenova explains.
Current, classical techniques cannot access this level of temporal resolution, leading to the averaged data that Mark worries about.
Getting accurate experimental data is only one half of the puzzle for Mark though. What also matters is the model itself. Usually, proteins are simulated using classical mechanics. But at the deepest level, everything is quantum. Therefore, there are currently certain protein structures and functions that can’t be modelled very well at all.
Mark hopes that quantum computing could solve this problem.
“People have been starting to dream about using quantum computers in the biosciences and particularly bioinformatics.”
Enter quantum computing
Professor Lloyd Hollenberg and his group at the University of Melbourne will be collaborating with Mark using their quantum simulations. As well as being a member of QUBIC, Hollenberg has been part of the Centre of Excellence for Quantum Computation and Communication Technology (CQC2T) since its inception.
Hollenberg has spent years thinking about how to use quantum computers for answering complex questions. “[I’ve been] looking at how you do these calculations in the context of the emerging technology,” he says.
Hollenberg and his group have already been able to simulate small molecules, such as water. But the next step is molecules that are biologically interesting.
A good first candidate could be something quite simple that contains a transition metal like iron, since “those sorts of atoms themselves are hard to understand because they’re quite complex”.
One of the main outcomes of QUBIC for Hollenberg, will be to identify the best general approach for the quantum simulation of any molecule.
“Once you have a really large-scale fault tolerant quantum computer that can handle very large molecules, what’s the best approach there?” Hollenberg wonders.
But quantum computing is not just for molecular simulation. Hollenberg is also collaborating with Professor Kim-Ahn Lê Cao, also from the University of Melbourne, who works on bioinformatics problems.
Bioinformatics deals with large data sets such as genetic studies containing thousands of people. But it can be a slow process running statistics on huge amounts of data. Quantum computing could speed up solutions.
“One of the first papers [I wrote] in quantum computing back in 2000, was to adapt the quantum search algorithm to the problem of sequence alignment in bioinformatics,” Hollenberg tells me. “That work’s been out there for decades now… more recently in the last year or two, people have been starting to dream about using quantum computers in the biosciences and particularly bioinformatics.”
It’s possible to take a new, experimentally identified, protein sequence and compare it to a database of sequences. It’s called “sequence alignment”. By looking for similarities between a new protein sequence and ones that have been seen before, it’s possible to predict structural and functional information without needing to actually solve the structure of a given protein.
The collaboration between Hollenberg and Lê Cao is a good example of how Centres generate collaborations that would otherwise not have happened. Although they work at the same university they had never met before the Centre proposal!
Inside our cells
Most of the time, when you want to understand how a cell works, you take a peek inside. The typical way of doing this is to create fluorescently-labelled proteins that you can view with a light microscope.
While this method has generated a wealth of information about every type of cell imaginable, it is also limited. Light microscopy and fluorescent tags only really offer visual information, showing where proteins are in the cell. But there are many other properties that a biologist might want to measure, such as viscosity (how a liquid flows), chemical species (forms), voltage, pH or temperature.
Associate Professor Irina Kabakova from the University of Technology Sydney is the leader of QUBIC’s cells theme. For the last 10 years, she and her lab have worked on Brillouin microscopy.
“It’s a technique which is using light, but we are looking at gigahertz phonons,” explains Kabakova. These phonons are quantum vibrations generated in a material, and they can provide information about the elasticity and viscosity of biological matter. “It’s a convenient technique to use because we are not dealing with any labels or adding anything extra to cells and tissues.”
Measuring elasticity and viscosity can reveal details about cellular remodelling. Remodelling is a dynamic process that happens regularly in cells, such as when 2 cells divide. It’s usually reversible but “sometimes it becomes irreversible and broken and then it’s usually linked to pathological disease conditions”. For example, a well-known feature of Alzheimer’s disease involves remodelling in brain tissue via a particular protein.
Kabakova and her team will use Brillouin microscopy to help biologists understand diseases that involve cellular remodelling, as a precurser to developing treatments. But to be most useful, Brillouin microscopy will likely be used in combination with other imaging techniques being developed in the Centre.
Associate Professor Irina Kabakova from the University of Technology Sydney is the leader of QUBIC’s cells theme. Credit: Courtesy of Associate Professor Irina Kabakova.
Correlating your photons
Professor Warwick Bowen is Centre director and a quantum optics specialist. His lab at UQ is creating new and improved ways of imaging cells, some of which use entangled photons.
Entangling your photons lets you create images with such high sensitivity that they can beat what’s called the “shot noise limit”.
This is the point at which the inherently random nature of photon emissions – the way light behaves – starts making an image too noisy or difficult to make out. It’s a consequence of quantum mechanics itself. But you can actually harness quantum laws to do better than the shot noise limit.
To get there, you need to generate quantum correlated light. In simple terms, quantum correlated photons provide a means of cross reference; a way to be more sure about when or where the photons you detect came from.
This is a win because, as Bowen points out, “light affects function, it affects structure, it affects viability of biological systems. So, you’ve got to worry about it. And people do worry about their photon budgets!” Turns out, quantum accounting is part of the deal.
Professor Warwick Bowen with Dr Igor Marinkovic. Credit: Courtesy of QUBIC.
Combining Brillouin microscopy with correlated photon imaging would be an example of what’s known as multiplexing (using multiple techniques at once). Multiplexing will be important for label-free techniques like Brillouin microscopy, because biologists will be able to see where inside a cell the signals are coming from and what proteins they are associated with.
Using this dual information, multiplexing will give researchers more certainty about cells and their contents.
It’s all part of the marathon effort required to understand and treat a wide range of diseases, from the aggressiveness of certain tumours to neurodegenerative diseases.
Thinking big
The final theme of QUBIC will try to reveal more about the brain, at the level of both small neural networks and whole living brains. Quantum tools that help us tease apart how the brain works can help us understand everything from the basis of thought to the reasons for neurological diseases and how to cure them.
In her lab at the University of Wollongong, Associate Professor Lezanne Ooi, leader of the brain theme, grows networks of patient neurons to study their neurodegenerative diseases. Ooi and her team take donated skin cells and turn them into neurons (brain cells). Because they’re from a specific person, they represent that person’s specific biology, bringing nuance to the research.
Ooi often measures the electrical activity of these neurons because that’s how they communicate. This can be done in a few ways – each with pros and cons – but often there is a trade-off between the time and spatial resolution that they offer.
But with QUBIC, Ooi’s lab will test a new quantum sensing technique, one that “has the potential to measure across every neuron and also over a long period of time. There’s opportunities there to increase both the spatial and temporal resolution.” It’s also non-invasive, meaning the neurons should, in principle, remain alive.
QUBIC researchers will also zoom out to consider how we can improve measurements of the whole living brain using magnetoencephalography (MEG). Like electroencephalography (EEG), which measures the electrical activity of the brain through electrodes attached to the scalp, an MEG measures magnetic activity.
Current MEGs rely on superconducting quantum interference devices (SQUIDs), which are a well-established quantum technology. The problem with SQUIDs though, is that they require cryogenic temperatures, think –268.9°C, to operate. As a consequence, MEGs are room-sized and they require the patient to sit absolutely still.
The devices are designed to detect magnetic activity, which is a direct result of the brain’s electrical activity. The resulting brain scans can then be used to understand neurological disease and brain function.
Both Bowen’s team at UQ and others at the University of Melbourne hope to improve MEGs by developing quantum sensors that can operate at room temperature. This new version has wires protruding at all angles and a 3D printed cap, reminiscent of a futuristic bike helmet.
Ooi is excited by what this could mean for patients. It presents “the opportunity to take diagnosis out of highly specialised facilities of which there’s only a couple in the country”. It also offers researchers a way to measure cognition in subjects as they move naturally and interact with their environment. Until now, this has been impossible with an MEG.
Associate Professor Lezanne Ooi from University of Wollongong, leader of the brain theme. Credit: Courtesy of QUBIC.
Now to deliver
These researchers are just off the starting blocks, with the Centre being established just a year ago. With these ambitious goals come weighty expectations.
“I was exceptionally excited when the Centre was funded, but there was also a lot of apprehension at the task ahead. I got into academia because I love doing research and it pulls your time away from that. Now I’m completely over that. The excitement has stayed and grown,” says Bowen.
They have just 7 years of funding to prove themselves. This sense of excitement is felt by all those involved but everyone has their own image of what a successful 7 years will look like.
“I would really like to be able to measure live cells in real time,” says Kabakova.
For Naydenova, it’s the idea that she could one day deliberately influence the behaviour of individual proteins. “I’ll actually be really excited to see a protein being controlled,” she says.
Ooi is thrilled to be part of this budding network of collaboration, but she recognises the pressure that a Centre can bring. “We obviously just need to make sure that we now deliver!”
Whether its impact is as grand as these researchers hope, only time will tell. But it’s clear that quantum biotechnology is off and racing at QUBIC.