01:25pm Friday 13 December 2019

Waikato students lead ground-breaking tuberculosis research

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Ground breakers: Waikato University science researchers, from left, Emma Littlejohn, Vic Arcus and Joanna McKenzie study results of an experiment.

For the last six years, Dr Arcus has headed a team studying a family of proteins from the bacterium responsible for the world’s most infectious disease – Mycobacterium tuberculosis.

TB kills around three million people every year, and is particularly bad in developing countries. In recent years it has made a resurgence in the Western world on the back of HIV.

 “When the bacteria get into your body, they immediately get attacked by the immune system, which bombards them with nasty chemicals and reduces their nutrient supply. Understanding how pathogens cope with this is crucial – and that’s essentially what these two are up to.”

Both women are looking at how proteins regulate the bacteria’s growth. Joanna completed her PhD last year, in collaboration with Otago University PhD student Jennifer Robson, and was capped just weeks ago.

“I would say that the paper we’re writing at the moment based on Jo and Jennifer’s work is the most significant I’ve ever been involved with,” he says. “They have shown that these proteins we’re working on are able to arm the bug with a mechanism for stopping growth and conserving nutrients.”

This dormancy makes TB a particularly difficult disease to treat, and is at the heart of Dr Arcus’s research programme. It is made more urgent because of multi-drug-resistant strains of TB emerging globally. “To me, this is the scariest statistic; that there are strains emerging which are resistant to all known antibiotics. If you get a resistant strain, then the treatment is the same that you would have got in the 19th century – you need to go to a sanatorium and, basically, hope.”

Joanna says her project was challenging. “No one had really worked on these proteins before, to the extent that we wanted. So I had to not only work with the proteins to figure out what they do, but I had to develop the method to be able to do that as well. It was a very long process, but once I nailed down the method, how to get the protein and to determine what it does, it all fell into place.”

Most bacteria only have a handful of toxin-antitoxin proteins; TB has 45. “The theory is,” says Joanna, “that TB has so many of these because they’re linked to its dormancy. For my PhD I was looking at one of these protein pairs to try and determine its function, and characterise the proteins to see what they do in the cell.”

She and Jennifer found that the toxin cuts RNA at specific sequences, and that those sequences are found in genes involved in sugar metabolism, which is needed for growth.

“These proteins are found in half of all bacteria. The mechanism they have uncovered looks like it could be applied not only to TB, but to other pathogens as well, which is fantastic,” he says.

Emma Littlejohn is into the third year of her PhD, and is studying a variation of the same project as Joanna. She is also looking at a pair of proteins. “One of which is a toxin,” says Dr Arcus, “and the other is what we call a helicase, which unwinds nucleic acid. Her work is two years behind Jo’s project, but I would expect that as she builds up evidence we will see general mechanisms emerging.”

Both completed their undergraduate degrees at Waikato, and were keen to study a medically based topic. Joanna says it’s good to see relevance in what is being worked on.

“It’s not that we had the idea that we were going to cure TB, or design antibiotics, but someone has to do this kind of work in order to get to that stage. It’s one more step in understanding the organism.”

They were among 23 New Zealand doctoral students awarded 2011 Claude McCarthy fellowships, worth $4000 apiece. This enabled them to attend overseas keystone conferences earlier this year – Joanna in Vancouver and Emma in California.

“I learned a lot about how current research is being undertaken, what techniques are being used and basically how they study that group of proteins. It was hugely beneficial to talk with others who are facing similar problems,” says Emma.

The team at Waikato have never worked on helicases before, Dr Arcus says. “Therefore it was very useful for Emma to attend a conference where she could find out what other scientists are doing. She is in the same position as Jo – she has to work out all these things for herself.”

The work requires resourcefulness and tenacity, he says. “You work in the lab every day and about two thirds of the things you do don’t work, and they don’t work for long periods of time. You need to deal with that fact, and you do this for four years. Results build up incrementally; it’s rare that there is a eureka moment. But at the end you have a body of evidence that leads to understanding general mechanisms. Which is how science progresses.”

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