Research Spotlights

By Georgia Barrington-Smith & Dr Rebecca Duncan

Medical radiation procedures, such as diagnostic imaging and radiation therapy, are critical in modern healthcare, providing life-saving detection and treatment tools for people suffering from diseases like cancer. Recent technological advancements have led to a new generation of radiotherapy treatments that promise to further enhance patient outcomes.

Developing radiotherapies

Unlike traditional radiation therapies that use large beams with broad target areas, microbeam radiation therapy (MRT) uses tiny, highly focused beams for more precise treatment. Unfortunately, traditional detection equipment cannot keep up with the steep dose changes and high intensities of MRT treatments; the small size and high intensity of the beams presents a considerable challenge in accurately measuring the amount of radiation being delivered to the patient. Therefore, there is a need to design a new generation of sensors with three key considerations:

1. Ultra-fine spatial resolution (down to the micron level),
2. The ability to mimic tissue behaviour in the human body to ensure accurate measurements across varying radiation energies, and
3. A high tolerance to radiation, ensuring the device remains functional even under the intense radiation levels associated with MRT.

Additionally, with real-time monitoring now mandatory in many countries to detect, evaluate, and correct radiation dose deviations during treatment, the sensors must be adaptable to the patient’s shape and provide immediate feedback.

Jessie helps develop highly specialised sensors

Consequently, Dr Jessie Posar, an AINSE ECRG recipient and 2022 AINSE Scholar Gold Medallist, along with her collaborators at ANSTO and the University of Wollongong, embarked on a research effort to develop wearable X-ray sensors that could monitor patients throughout their treatment to track radiation dosage.

The sensors were crafted from a carbon-based flexible material mounted on a specialised plastic film called Kapton, which was selected for its superior durability and flexibility compared to commercially-used polyethylene (PE). The sensor was designed with a very thin layer (260 nanometers thick, about 200 times thinner than a human hair) composed of two organic materials: P3HT (a polymer) and o-IDTBR (a special chemical compound). The sensor was connected to two types of metal contacts—Indium Tin Oxide (ITO) at the bottom and Aluminum at the top—to measure the X-ray signals.

To test the effectiveness of this new sensor, the team developed a custom-made system to read the sensor data in real time. The sensors’ response was then evaluated using the Imaging and Medical Beamline at ANSTO’s Australian Synchrotron, one of only two places in the world currently developing MRT technology.

Testing the feasibility of the X-ray sensor

Using multiple filters to adjust the energy of the X-ray beams to track the sensor’s responsiveness, the team discovered that when the sensor was mounted on Kapton film, it was sufficiently sensitive to accurately measure the required radiation doses with high spatial resolution. However, the team also detected that the Indium Tin Oxide layer was interacting with the incoming beam, which in turn negatively impacted the sensor’s performance.

Further testing revealed that using polyethylene instead of Kapton, caused the sensor to perform less efficiently because the current from the sensor flipped direction during testing, making it unreliable. They determined that the polyethylene caused a build-up of electrostatic charge at the interface between the polyethylene and the organic material, which interfered with the sensor’s performance. This problem was not present when Kapton film was used.

How robust is the sensor?

Next, the team tested how well the sensor could handle high levels of radiation. Overall, the sensor performed moderately well, showing a performance drop of approximately 35% when exposed to high doses. This is a significant improvement over previous radiation hardness studies on existing devices that showed performance decreases of 65%. This reinforced the new design as being more durable than pre-existing sensors.

Jessie’s research demonstrates the development of a new kind of sensor that could help make radiation treatments even more precise and safe. These sensors could improve future treatments for diseases like cancer by providing a means of monitoring the doses associated with new precise, high intensity therapies such as MRT, making the procedures safer and more effective.

AINSE are proud to spotlight Jessie Posar for her outstanding work!

To explore more incredible research by our AINSE scholars, visit ainse.edu.au/research-spotlight.

Don’t take your finger off the pulse as we bring you our next article in Medical March, showcasing the wonderful work of Samantha Alloo, who investigates the use of multi­­­modal signals to uncover high-resolution details in clinical X-ray scans.

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By Georgia Barrington-Smith & Dr Rebecca Duncan

The agricultural industry is constantly under threat from fungal pathogens that infect important plant crops like tomatoes, bananas, and cotton. In response, plants have developed new defence mechanisms, fuelling an ongoing arms race against these invaders as they, in turn, develop new ways to circumvent these defences.

How the fungus fights…

During infection, the fungi secrete hundreds of proteins, called SIX effectors, into the plant’s vascular system. These effectors damage the plant’s immunity, physiology, and structural integrity. In response, plants have evolved immune receptors that recognise a subset of these SIX effectors, called Avr effectors, and then trigger an immune response.

While many fungal effectors have been studied, to date only one has had its structure fully determined: an effector from the tomato pathogen Fusarium oxysporum f. sp. lycopersici (FOL), known for causing tomato vascular wilt. Understanding how plants recognise Avr effectors is critical for developing crops resistant to fungal disease. However, understanding how these effectors work has been difficult, as they don’t resemble proteins with known functions.  

Daniel’s contribution to the arms race

As the function of a protein is highly dependent on its 3D structure, Daniel Yu, an AINSE PGRA scholar, with his collaborators at ANSTO and the Australian National University, used X-ray crystallography on the MX1 and MX2 beamlines at ANSTO’s Australian Synchrotron to determine the 3D crystal structure of three significant fungal effector proteins: Avr1 (SIX4), Avr3 (SIX1), and SIX6.

While investigating the crystalline structures, the team discovered that although these proteins share less than 20% similarity in their amino acid sequences, they have a similar overall structural shape (or “fold”). These three proteins are the first known examples of fungal effectors that are made up of two distinct domains, which are functional regions of the protein. The discovery of these structures is significant because they represent a new group of fungal effectors called the FOLD (F. oxysporum f. sp. lycopersici dual domain) effector family.

Understanding these structures has provided insights into how plant immune receptors recognise fungal effectors. For example, Avr1 is recognised by the ‘I’ receptor in tomato plants, which triggers a defence response that prevents the fungus from spreading. There are two forms of the ‘I’ receptor in different tomato varieties: one that is resistant to the pathogen and one that is not. Interestingly, both receptor types can recognise a similar effector from a different strain of Fusarium oxysporum that affects watermelons.

To understand the details of how the ‘I’ receptor recognises Avr1, researchers created mixed proteins by swapping parts of Avr1 with similar proteins from the watermelon pathogen. Analysis of these mixed proteins identified one key part of the protein that was crucial for effector recognition. This insight could help design modified plants with enhanced resistance to fungal pathogens.

The ongoing fight against fungi!

Unfortunately, in the ongoing arms race between fungi and plants, certain fungal pathogens have gained the upper hand by changing their amino acids to evade recognition by a plant’s immune receptors. This means that plants with the evolved immune receptors, which had previously helped them resist pathogens, are now at risk once again from fungal infections.

Thankfully, Daniel’s new understanding of plant response to Avr effectors can give plants the upper hand in the arms race. By using gene editing approaches, scientists may be able to modify the defeated immune receptors to restore their Avr recognition and resistance. This will help in the development of disease resistant crops to proactively protect from pathogenic threats, with enormous benefits for our food supply and the agricultural industry.

AINSE are proud to spotlight Daniel Yu for his scientific contribution!

To read more research spotlights visit ainse.edu.au/research-spotlight.

And that’s a wrap on our Fungi February series, but don’t worry we will be back with some exciting research in Medical March as we uncover the marvellous mysteries in nuclear medicine.

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