John Silke is a Theme Leader at WEHI, and is particularly interested in how inflammation is linked to cancer and other diseases. He has been Relaying with Team WEHI since 2019, when he came to the arena straight off an international flight to do his walking shift at 1am!
What do you do?
I supervise my students and postdocs to make discoveries for me and for them. My job involves a lot of reading literature, and a lot of thinking about why some people’s experiments get the results they do, and why some experiments we do don’t seem to work – and being very happy when some of our experiments do work!
What are you working on?
Many, many years ago I started looking at these proteins called inhibitor of apoptosis proteins (IAPs). By their name, some people will recognize that they work to inhibit cell death, which is very important in development and cancer and all these sorts of things. The idea at that time was that these IAPs helped keep cancer cells alive. So we wanted to understand how they did that, with the idea ultimately of being able to use that knowledge to kill cancer cells: Stop the proteins that are keeping the cancer cells alive, and you can kill the cancer cells.
So a few years later, when we’d made some discoveries about the way these proteins worked, we partnered with a drug company, who had developed inhibitors of these proteins that could, they hoped, be used to kill cancer cells. And indeed they did, and they are still being tested in clinical trials – still being tested because they don’t work in the simple way we had thought they would.
So while these drugs are not available on the PBS, they are nevertheless a really fantastic tool, because they enabled us to really look at how these proteins worked in cells without any fancy tricks – we just added our drugs and then looked at what happened in the cells. So all of a sudden we got this new view of how this proteins work. And it’s really quite remarkable. They do indeed keep cancer cells alive, but it’s a very complicated mechanism. In fact, it’s so complicated that many people that know me think whenever I try to explain the pathway that I’m being deliberately complicated! But that’s not true, the pathway really is extremely complicated…
[Editor: He’s not kidding, it really is complicated… ]
Essentially, IAPs inhibit inflammation. And in some cases once they’ve inhibited that inflammatory response, they also protect cells from cell death. So if you can switch off or inhibit these IAPs, you get more inflammation, and you also get more cell death.
And you might say, “Why on earth would that happen?”. Well, we think that this happens normally in infectious diseases, where there will be inflammation induced by the pathogen. And some cells are going to be in a precarious position, they might be infected by the pathogen, and therefore it’s important that those cells should be killed off. So it’s quite a clever system to integrate inflammation and cell death. I think it has a lot of physiological relevance, but it does make it very difficult sometimes to work out chickens and eggs.
What got you interested in science? And this in particular? Where did you start?
A long, long, long, time ago! My mum was a science teacher, and I think a certain amount comes from that. My dad was a failed agricultural scientist, but went on to become an accountant, so you can see there’s a certain facility with maths. But really it was love of the natural world and biology. And a famous family story is that at a very young age I was collecting those little cards that come with something from the supermarket, that you could stick in a book, and there were 100 animals I think. I read one of these cards, and it was meant to be the fastest fish, but they got it wrong. And my mum helped me to write a letter to these people, and they acknowledged it and said, yes, you are right, and thank you very much. So I’ve always been out there trying to correct the scientific literature from an very early age!
But you can see the fact that I was so familiar with animals and their characteristics, there was some sort of interest in biology there.
A question from Justin (12): How do you feel doing your job, and what is your favourite topic in science?
When I wake up in the morning and I come to work straightaway at 6am – it takes me about five or ten minutes to come into work – I really enjoy it. I look forward to the rest of the day and I start reading papers and learning about new things and learning more about the things that I do work on. As the day wears on, I have hundreds of emails to answer, forms to fill in and other things, and towards the end of the day I am a little less excited! But the best bit is at the beginning of the day, when I think I’m probably going to be working on science. It’s just that reality sometimes gets in the way.
As for my favourite topic, the easy answer would be to say it’s what I work on, it’s really inflammation and cell death and cancer and how all that integrates and works together! But I think I would have been happy and excited by any of it – astronomy or anything. I read about the Mars Rover, or I read about engineering challenges, or climate science, or archeology and anthropology, and I think wow, that’s really cool. All those things, I just love it all. It’s about trying to understand the world we live in, and I think all of those questions are intrinsically interesting. I do find my own topic easily able to capture my attention and interest for a long time – I don’t get bored with it! But I do get excited about other science.
What’s the best thing about doing science?
The number one thing for me is that the science is the boss. You have to do what the experiments tell you to do, so it’s somehow a very different pressure to what many people feel. The pressure comes from trying to find things out, it’s not anything else or anyone else. There are other pressures, like getting money and stuff, but principally what drives you, your boss, is trying to understand the problem, and that’s a good boss to have.
And I think the other thing is that scientists as a group are wonderful, varied, interesting people from many different nations and it’s always fascinating to work together with fellow scientists. I think in my lab, there were 8 of us having lunch yesterday, and we had lived in or been born in or our parents had lived in something like 24 countries. Out of eight people! And that gives a very interesting perspective on the world.
Why do you relay?
I am very passionate about fitness, I think it’s probably the best way to remain healthy and live a long happy life, so I’m really passionate about any type of exercise and fitness activity. I encourage my lab members to exercise. I’m the type of boss that’s not saying they need to stay longer at work, I’m the type of boss who says you really should do some exercise today, and then you can finish your work after that.
But the other point of course is that the Cancer Council do fund my research and I’m incredibly grateful for that. I’m more than happy to put back in to supporting and advertising and spreading the message that this is a good charity to support.
Team WEHI Relay for Life 