Diagnostics
body, serving as structural components in cells, catalysing biochemical reactions, and regulating gene expression. They are also essential for processes like muscle contraction, cell signalling, and immune responses. Even this conversation we’re having, Alexandrov expands, is possible because proteins are turning on and off in our brains and performing sophisticated information processing at the millisecond scale. For Alexandrov, this is the beauty of biology. Unlike an industry such as electronics, where engineers developed relays, switches and vacuum tubes without knowing that an iPhone would come out of it one day, in biology, we know what the product looks like. We live in it every day. “What we don’t know is how much time and money it will take us to replicate or to build the technologies and the industries that can deliver the performance on the same scale,” Alexandrov says. “But ultimately, biotechnology is an exercise in reverse engineering.” He believes that he and his QUT colleagues have made an important step towards building artificial protein machines with diagnostic utility, a breakthrough that was published in the journal Nature Nanotechnology. The paper describes a new approach for designing molecular ON-OFF switches based on proteins. “What we’re doing is trying to create protein-based machines that we can train to recognise something that we would like to detect and then give us a signal that we can understand – basically we’re building biological transistors,” Alexandrov explains. “The challenge is using our extremely basic protein engineering skills to build these things to specifications. Historically, biotechnology has been an act of trolling nature, finding things that are doing kind of the right thing and then building the hardware, chemistry and software around them to get what we need.”
Improving the existing standard of care The example detailed in the research to demonstrate the technology focuses on a cancer chemotherapy drug methotrexate that is toxic and requires regular measurement to ensure patient safety. If too little of the drug is delivered, the cancer will survive, but too much of it could kill the patient. The sensor Alexandrov and his colleagues designed for the drug uses a colour change to identify and quantify the drug. It’s been a long road to reach this point, with one lesson standing out as particularly painful. Ten years ago, when Alexandrov first discovered the potential of the research he and his colleagues were carrying out to develop protein switches, he got a little over- excited. “We thought, brilliant, this could solve the problem of personal diagnostics, and we rushed to commercialise the technology,” he recalls. This was
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www.practical-patient-care.com
about the time Theranos was hitting the headlines with its lab-on-a-chip technology, which founder Elizabeth Holmes promised could run hundreds of tests in a doctor’s office on a single drop of blood. She was ultimately proven to be a fraud and sentenced to more than 11 years in prison. “For our part, we realised that, while our technology was real, we had very little idea about how the diagnostic industry works and couldn’t answer very basic questions, such as: Who would our customers be? What are the market forces? What do regulatory bodies want? How much does it cost to build an integrated diagnostic company?” Alexandrov admits.
Alexandrov’s team is prioritising getting their first synthetic switch to patients while continuing research for future advancements.
“What we’re doing is trying to create protein- based machines that we can train to recognise something that we would like to detect and then give us a signal that we can understand – basically we’re building biological transistors.” Professor Kirill Alexandrov
He decided to take a different tack the second time round. Rather than attempting to put a catch- all handheld diagnostic device on the market, they identified a real issue healthcare providers needed to solve. Sophisticated and expensive lab equipment for therapeutic drug monitoring is often unavailable in remote areas in Australia for economic and logistical reasons. “If we could provide a smart kit that could provide an answer for those patients on how their drug is performing without the need for expensive equipment, so clinical practitioners can decide where to go with the therapy, we could contribute to improving the existing standard of care,” Alexandrov explains. The next step is for the sensor to be tested in Queensland Health laboratories for use in a clinical
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