Researchers from the Queensland University of Technology (QUT) have devised a cutting-edge approach to designing molecular ON-OFF switches based on proteins, with vast implications for biotechnological, biomedical, and bioengineering applications. This pioneering technique promises to revolutionize the development of faster and more accurate diagnostic tests, enabling the detection of diseases, monitoring water quality, and identifying environmental pollutants with heightened precision.

Led by Professor Kirill Alexandrov from the QUT School of Biology and Environmental Science, the research team has made strides in the CSIRO-QUT Synthetic Biology Alliance and is associated with the ARC Centre of Excellence in Synthetic Biology. Their findings, published in Nature Nanotechnology, underscore the predictability of engineering protein switches through their innovative "protein nano-switch" method.

Currently, "point-of-care" diagnostic tests like blood glucose, pregnancy, and COVID test kits utilize protein-sensing systems to detect specific substances, such as sugar, pregnancy hormones, and COVID proteins. While these tests have proven invaluable, Professor Alexandrov emphasizes that “these, however, represent only a tiny fraction of what is needed in a patient-focused healthcare model.”

The newly devised "protein nano-switch" method offers a modular system that resembles building with Lego bricks, providing the flexibility to easily replace components to target different substances, such as drugs or medical biomarkers. This versatility enables accelerated development of various diagnostics, significantly reducing time and enhancing success rates in creating essential testing kits for human and animal health, water contamination assessment, and even rare earth metal detection in samples to direct mining efforts.

Collaborating with experts from various disciplines, the multidisciplinary research team includes lead researcher Professor Kirill Alexandrov, Dr. Zhong Guo, Cagla Ergun Ayva, Patricia Walden, and Adjunct Professor Claudia Vickers from QUT. Additionally, the team collaborated with prominent electrochemists Evgeny Katz and Oleh Smutok from Clarkson University in New York, as well as chemical pathologist Dr. Jacobus Ungerer from Queensland Health.

To demonstrate the efficacy of their technology, the team focused on developing a sensor for a cancer chemotherapy drug, requiring precise measurement due to its toxicity. By utilizing a color change mechanism, the sensor successfully identified and quantified the drug, showcasing its potential for real-life diagnostic applications.

Dr. Jacobus Ungerer said, “This has the potential to improve and expand laboratory testing, which will result in substantial health and economic benefits.” 

Looking ahead, Professor Alexandrov envisions two key directions for their research. Firstly, the team aims to develop computer models that can expedite and enhance the design and construction of protein switches. Secondly, they plan to demonstrate the technology's scale and potential by building numerous switches tailored for different diagnostic applications.

Describing the new technique as bestowing scientists with “unprecedented control over the construction of protein-based sensing systems,” Professor Alexandrov looks forward to further refining the approach, standardizing it, and scaling it up to create more sophisticated sub-systems. The future prospect of designing components from scratch could potentially open up new frontiers in biotechnological advancements.

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