Published Nov 9, 2018
A fundamental research project into enzymes has led to a discovery that could improve the way labs all over the world analyse glutamine.
Glutamine is the most abundant amino acid in the human body and is a key fuel source for rapidly dividing human body cells, particularly in the immune system and intestinal lining.
From a medical perspective, abnormal glutamine levels can indicate metabolic diseases such as urea cycle disorders, over-training syndrome in athletes, or neurodegenerative disorders such as muscular dystrophy. Low glutamine levels may also indicate the presence of cancerous tumours, which frequently use glutamine as their primary energy source.
From a research perspective, glutamine is an essential energy source for growing human and animal cell cultures in flasks or dishes—the core of bio-manufacturing therapeutic proteins and viral vaccines. However, while too little glutamine is detrimental, so is too much, as excessive levels in a culture medium can generate toxic levels of ammonia.
“There’s a real need for medical, research and industry laboratories to be able to measure glutamine in a quick, economic and accurate manner,” says David Ackerley, Professor of Biotechnology in Victoria University of Wellington’s School of Biological Sciences, and leader of the team behind the research.
He says the ‘gold standard’ currently used for glutamine measurement involves expensive, specialised instruments which are unwieldy, and unsuited to the rapid turnaround of samples. As a consequence, many different companies offer enzymatic kits, which are simpler to use and far more cost-effective.
“All these existing kits require glutamine to be converted to glutamate before it can be measured. This means you also have to establish how much glutamate was in your starting sample, and then subtract that value from your measurements. These extra steps substantially increase the amount of error, as well as the likelihood of cross-sample contamination.”
In contrast, David says his team has developed a proprietary enzymatic process that offers simple, direct measurement of glutamine across a diverse range of biological samples, including cell culture media and blood.
“Unlike other diagnostic kits, we are able to convert glutamine directly into a measurable product—eliminating the need for that second step to remove glutamate,” says David.
He says their technique involves direct conversion of glutamine into a detectable blue pigment that can be seen and measured using standard laboratory instrumentation. “Our test is faster, more sensitive and because the enzyme is stable, it doesn’t need to be transported in ice which translates to even more cost-savings.”
Alistair Brown, whose PhD thesis focused of the biotech applications of the enzyme, says that it’s the ability to get colour output from the blue pigment—“so that lab technicians can immediately see any reaction on a molecular scale”—that makes their invention unique and, ultimately, a commercialisable product.
“We approached Viclink and said ‘Hey, we’ve got this test we’re developing, we think it might have some commercial potential’,” says Alistair. “They jumped on board really quickly and not only provided us with additional funding so we could patent our intellectual property, they have also been investigating possible industry partners in New Zealand and overseas.”
He says the team is now focused on the product development of a glutamine sensing kit, so that they can manufacture and sell the kits directly to other laboratories.
David says that while it’s important to make research discoveries with a particular goal or problem in mind, this project proves that fundamental research also feeds the pipeline of new ideas with commercial potential. “Both fundamental and applied research are equally important for the University’s future commercialisation opportunities.
“We’re already working on how we can use our enzyme research in other areas—for example, we are working with Associate Professor Wayne Patrick to develop biosensors for New Zealand winemakers, while there’s also potential for our enzymes to be used in the development of a new class of antibiotic to combat the growing resistance to current antibiotics.”
For more information, email Jeremy Jones.