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Ancient wallaby protein is a powerful antibiotic

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Matt Smith:

Welcome to a La Trobe University podcast. I would be your host Matt Smith and my guest today is Ben Cocks, Research Director of the Bio-Sciences Research Division at the Department of Primary Industries and a Professor in Animal Genetics and Genomics at La Trobe University. Thank you for joining me Ben.

Ben Cocks:

Oh, thanks Matt.

Matt Smith:

Now, you've been working with DNA from a 60 million year-old wallaby to combat drug-resistant bugs or pathogens. Can you tell me a bit about that?

Ben Cocks:

Well, what we've done is actually do some analysis of the wallaby genome which was recently published, and identified a number of genes encoding anti-microbial peptides and in terms of ancient DNA, what we've been able to do is actually reconstruct in some cases what the ancestor of Australian marsupials, what a certain segment of DNA would have looked like 60 million years ago when Australia was part of Gondwana.

Matt Smith:

Did you start with a problem where you're looking for something to combat antibiotic resistant bugs and work from that?

Ben Cocks:

We were very interested in the immunity that are in platypus and wallabies because both these animals when they're born don't have an adaptive immune system – they can't make antibodies until they're, in the case of the wallaby, a hundred days old, yet they're able to avoid infection for example, in the pouch, which has lots of microbes. We were interested in what was giving the animals this type of immunity and it turns out that they do have these antimicrobial peptides and in the genome we can actually see the many different versions of these antimicrobial genes.

Matt Smith:

And these antimicrobial genes and the peptides, they're good at combating bugs.

Ben Cocks:

They're not bugs, they're bacteria, but yeah, especially, it turns out that one particular one that we've studied extensively that's found in wallaby milk in the early stages of lactation, is very potent against multi-drug-resistant bacteria and in fact up to ten times more potent than drugs like tetracycline and ampicillin and we've actually tested the clinical isolates from Australian and American hospitals which are actually resistant to all available antibiotics, and the peptides were very effective against those particular bacteria.

Matt Smith:

Did it surprise you that these wallaby genes had applications outside of a wallaby?

Ben Cocks:

The normal function I guess appears to be in protection of the pouch young – they're also expressed in the skin, but one of our colleagues at the University of Melbourne, Marilyn Renfree, was able to actually do some profiling of the bacteria that are normally in the wallaby pouch, and many of them are actually close relatives to some of these hospital superbugs, like klebsiella and pseudomonas, so in the light of those results it's probably not that surprising that they're effective against those types of bacteria.

Matt Smith:

You took it a step further from the modern-day wallaby and you reconstructed the gene of a 60 million year-old wallaby. Now, why did you do that? Did you do that expecting to find a difference in the resilience?

Ben Cocks:

Well, we thought it was interesting that we had this gene family, in this case five different genes which had clearly been duplicated from an ancestral gene, so we were very interested in what the function of the ancestral gene would have been and I guess we thought it might have had broad based activity for I guess it to be utilised in evolution over that time, so I guess the fact that it also coincided with the timing when the ancestor of all Australian marsupials existed was also interesting to us, and sure enough, when we tested it, not only did we find that it actually worked, which was very nice, validating the computational methods, but also that it was very effective and in fact quite effective against mastitis pathogens, which we'd tested. We actually think that may be a possibility in terms of the primordial function could have been to protect the mammary gland as well as pouch young.

Matt Smith:

So what does that indicate about the 60 million year-old wallabies? Were they stronger animals?

Ben Cocks:

It's hard to know what the full context of the gene is in that time frame and the animal that is closest to that ancestor is djarthia which has been identified fossils that are 55 million years old in Tingamarra in Queensland. These animals are small possum-like animals and appear to share features that indicate that their potential ancestor and Michael Archer's group at the University of New South Wales has discovered these, and so we think these animals would have had a pretty unique set of immune functions and this is just part of that puzzle of what they had.

Matt Smith:

I was interested in the thought that, could you take that one step further and use that gene to grow yourself an ancient marsupial?

Ben Cocks:

As I've mentioned, it's really just one gene, but it is quite nice that we can actually use genomes and computational methods now to be able to predict some of these genes. I guess if that continues in terms of the genomes being available and the techniques, we may in fact be able to re-create some of these genes and then introduce them back into animals at some point, but that would be a trillion dollar experiment.

Matt Smith:

But it's still, it's a first step in that experiment, isn't it?

Ben Cocks:

I think it is potentially it is a first step in being able to do something like that, and note that Marilyn Renfree's group at the University of Melbourne were actually able to take a Tasmanian Tiger gene and have it expressed appropriately in a tissue-specific manner in a mouse, so you could actually combine that idea with computationally re-creating ancient genes, that's definitely a possibility.

Matt Smith:

OK, that's good. I just want to know that I'm going to get my stegosaurus one day. One thing that I do want to know is now that you've done this, are you looking to apply similar techniques to say, platypus, to see what you could find?

Ben Cocks:

Well, there's a lot of options available in terms of different genes and certainly our colleagues at the University of Sydney, led by Kathy Belov, are interested in some of the anti-microbial gene families from that perspective. At the moment, we're actually working on some of the modern-day peptides, as they appear to be very effective, and then I guess incorporating some of the advantages of some of the computationally predicted peptides in proving what we have as potential therapies. That's probably our focus at the moment.

Matt Smith:

What's going to be the practical application of this?

Ben Cocks:

Well, the two areas that are showing the most promise is one in mastitis, which is a big problem in the dairy industry and could be part of the natural function in the marsupials and maybe that can be a therapy for mastitis which is a costly problem for the industry. In the US, it's calculated to be 1.8 billion a year lost in mastitis and in Australia it's in the tens of millions in losses, and obviously a big hassle for farmers. The other application is obviously the multi-drug-resistant bacteria where there's a possibility the peptides could be developed as an intravenous for people having infections that are resistant to available antibiotics.

Matt Smith:

AgrioBio opens early next year. Have you picked your desk out yet?

Ben Cocks:

There's a certain area, where, yep, I've got an office, which looks out over the canopy and the university, which will be a nice change because I'm in an office that doesn't have natural light at the moment. But yes, the facilities just look fantastic. And most importantly, the labs have a very nice environment to get some good work done.

Matt Smith:

That's all the time we've got for the La Trobe University podcast today. If you have any questions, comments or feedback about this podcast, or any other, then you can send us an email at podcast@latrobe.edu.au. Professor Ben Cocks, thanks for your time today.

Ben Cocks:

Thanks Matt.