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When Cells Rebel: the dark side of evolution

I love dystopian horror. I love to relish in the thrill of disgust from the comfort of safety – a comfort bolstered by the knowledge that such grotesquerie could never actually happen in real life. Zombies don’t exist. Monsters aren’t trying to escape from the underworld. Cancer isn’t contagious. Actually, maybe scratch that last one. . .

You see, nature may not have the imagination of Stephen King, but it does have something even more powerful in its arsenal: mutations. Mutations are to evolution what creativity is to horror writers – the raw material that allows them to conjure up new and wondrous forms. From the most beautiful (buttercups, butterflies, butter yellow bumblebees) to the most horrific (flesh eating bacteria, pandemic inducing viruses, cancer cells).

Evolution favours the fittest individuals, be they butterflies or bacteria. In this case, “the fittest” just means the ones that are most successful at reproducing. If we are talking about koalas, reproduction means making cute little baby koalas. Everyone likes those. But when we’re talking about cancer cells, reproduction means growing and spreading and killing one’s host. Nobody likes that. Even the cancer cells probably wouldn’t like it – because killing their host also means killing themselves in the process. Kind of like a suicide bomber without the political motivation. But evolution is blind to morality and selects for the cute little baby koalas and murderous cancer cells equally – whatever is most efficient at making more copies of itself. Survival of the fittest.

Mutations are constantly arising in nature. Sometimes these make more successful versions of things, sometimes less successful. It’s a bit of a trial-and-error process. And somewhere in that trial-and-error process, a handful of cells have stumbled across the secret to become the most successful cancer cells ever. Super-cancers! How? By finding a sneaky way around that whole unfortunate dying-when-your-host-dies bit.

They do this by taking a leaf out of the life history book of parasites. Like cancer cells, many parasites are reliant on a host to survive. But unlike cancer cells, many parasites have the power to survive the death of their host by simply finding a new host – a power that evolution has also bestowed upon these super-cancers.

Yes, nature has managed to take one of the most awful diseases known to humanity and done perhaps the only thing that could make it worse. It has made it contagious.

Thankfully, such contagious super-cancers are mercifully rare and none of them affect humans (yet). But the rest of the animal kingdom has not fared quite so well. Leukaemia cells drift through the sea like hidden assassins, spreading from one unsuspecting clam to the next. Dogs can get mushroom shaped tumours on their penises from sex with a poorly chosen partner. And one of our most iconic Australian animals, the Tasmanian devil, is at risk of extinction from not only one but two contagious cancers (creatively named Devil Facial Tumour Disease 1 and Devil Facial Tumour Disease 2). Sometimes lightning really does strike twice.

The good news is, this is where we come in. By researching Devil Facial Tumour Disease – one of the most uniquely horrifying and bizarre diseases to ever arise – we aim to understand how it works, how it spreads, how it evolves and, hopefully one day, how we can stop it.

Follow me for more fun and uplifting facts about the animal world!

Patra Petrohilos (PhD Student) is researching the evolution of devil facial tumour disease (DFTD). By investigating anticancer properties of naturally occurring peptides, she is aiming to identify novel agents with therapeutic potential against DFTD. Patra Petrohilos is a PhD student with the Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS). Follow their exciting research at https://cipps.org.au.

Tasmanian devil cathelicidins exhibit anticancer activity against Devil Facial Tumour Disease (DFTD) cells

Type: Journal Article

Reference: Petrohilos, C., Patchett, A., Hogg, C.J. et al. Tasmanian devil cathelicidins exhibit anticancer activity against Devil Facial Tumour Disease (DFTD) cells. Science Report 13, 12698 (2023). doi: 10.1038/s41598-023-39901-0

Abstract

The Tasmanian devil (Sarcophilus harrisii) is endangered due to the spread of Devil Facial Tumour Disease (DFTD), a contagious cancer with no current treatment options. Here we test whether seven recently characterized Tasmanian devil cathelicidins are involved in cancer regulation. We measured DFTD cell viability in vitro following incubation with each of the seven peptides and describe the effect of each on gene expression in treated cells. Four cathelicidins (Saha-CATH3, 4, 5 and 6) were toxic to DFTD cells and caused general signs of cellular stress. The most toxic peptide (Saha-CATH5) also suppressed the ERBB and YAP1/TAZ signaling pathways, both of which have been identified as important drivers of cancer proliferation. Three cathelicidins induced inflammatory pathways in DFTD cells that may potentially recruit immune cells in vivo. This study suggests that devil cathelicidins have some anti-cancer and inflammatory functions and should be explored further to determine whether they have potential as treatment leads.

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Holidays in the Sun

by Patra Petrohilos (PhD Student) 

I am not a seasoned traveller.

I can count the number of times I have been on a plane on my fingers. The only time one of those planes took me overseas was 20 years ago.

Then I heard about a summer school that was being held in Cambridge on the evolutionary biology and ecology of cancer. When my supervisors suggested I apply to attend, I reacted pretty much as if they’d suggested I apply for the first manned mission to Mars. That’s the kind of amazing thing you fantasise about. Not the kind of thing you get to do in real life.

Despite my unworldliness, I had heard of Cambridge. I knew it was home to the third oldest university in the world – one so old that it predated the Aztec Empire. And I knew it was “a long way away”. But it wasn’t until I was sitting on a plane for fourteen hours straight (and then a second plane for an additional seven hours) that I appreciated what “a long way away” actually meant.

“How long was your flight?” a European PhD student asked me soon after I arrived.

“Well, the first one was fourteen hours.”

I’m not sure what shocked her more – the fact that I’d had to endure a fourteen-hour flight, or the fact that after such obscene amount of time I was still only partway to my destination. Either way – it was reassuring to not be the only one who hadn’t realised just how far “a long way away” can actually be.

And so began one of the best weeks of my entire life:

There were morning walks through the lush forest.

SquirrelThere were squirrels frolicking in the greenery. Like an Enid Blyton book come to life!

Dining Hall and foodThere were fancy meals in even fancier dining halls. I basically spent my days pretending to be a rich character in a Jane Austen novel.

Pub

There were pints of beer in 16th century pubs shared with new friends from all over the world.

New friends with job descriptions I didn’t even know existed! (Exciting and exotic sounding things like “fish vet” and “mathematical oncologist”). I told them excitedly about my project and listened, enthralled, as they told me about theirs. We attended workshops on evolution and mathematical modelling and game theory and applying landscape ecology methods to cancer research.

But back to my favourite part – those 16th century pubs. I was determined to try all the exotic British foods that I only knew from books – toad in the hole, black pudding, pickled eggs. Pickled eggs! Imagine my delight to see an entire jar of them glistening temptingly behind the bar.

“Would you like the full experience?” the bartender asked me.

When someone asks if you want the full experience, the answer is always “yes”. In this case, the full experience turned out to be crushing up a bag of salt and vinegar chips before rolling your pickled egg in the salty, sour, crunchy crumbs of pure deliciousness.

Pickled eggs - Salt and vinegar chips

I clutched my English delicacy with glee as I eagerly headed back to our table. For some reason, my new friends looked slightly less excited with my find than I was. Their facial expressions spanned the entire gamut of confusion, from shock to amusement to admiration at my bravery. Evidently, they were fellow foreigners like me, I told myself, unfamiliar with the fineries of traditional English bar snacks.

And then – “I have never in my life seen anyone actually order a pickled egg,” a lovely English doctor announced.

Ok so maybe it was less a British delicacy and more something they tell stupid Australian tourists. It was still delicious.

Cambridge had a magic that I had thought only existed in literature. The entire trip felt like falling into the pages of my favourite childhood books, like I had finally been handed my letter from Hogwarts. I was Alice in a wonderland of history. I saw baby swans as I went punting down the Cam River.

I was thrilled to drink beer at the Eagle – that famous Cambridge pub where the structure of DNA was first announced. I was even more thrilled to see that someone had the gumption to add Dr Rosalind Franklin’s name to the plaque out the front.

I even loved the charming signs telling me to wash my duvet.

I returned to Sydney, energised and inspired; armed with a renewed fervour to attack my PhD. I can’t wait to carve out my own tiny sliver of novelty in the monolith of human knowledge so that I can tentatively place it upon the shoulders of the giants who came before me. Thank you so much to my supervisors Professor Kathy Belov, Dr Carolyn Hogg and Dr Emma Peel for making this happen.

Author:

Patra Petrohilos (PhD Student) is researching the evolution of devil facial tumour disease (DFTD). By investigating anticancer properties of naturally occurring peptides, she is aiming to identify novel agents with therapeutic potential against DFTD.