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The immune system – friend or foe?

Professor GoodnowProfessor Chris Goodnow

14 May 2010

The problem with tackling autoimmune disease, says 2010 NHMRC Australia Fellow, Professor Chris Goodnow, is our lack of understanding of why the immune system sometimes attacks a healthy part of the body.

Here Prof Goodnow explains to Carolyn Norrie how his Australia Fellowship will enable his research team to shed some light on that problem. Along with investigating the genetic differences between people with autoimmune disease and those without, they hope to create essential treatments for clinics of the future.

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Transcript of podcast

Voice-over:  Welcome to this National Health and Medical Research Council podcast. Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.

Introduction: Hello, I’m Carolyn Norrie and I’m talking to one of NHMRC’s 2010 Australia Fellows, Professor Chris Goodnow of the Australian National University.

Interviewer: Chris, congratulations on your Australia Fellowship.

Prof Goodnow: Thank you it’s fantastic.

Interviewer: You’re working in the area of autoimmune disease. Would you like to tell us a bit about that?

Prof Goodnow: I guess to start with, autoimmune diseases affect about five percent of Australians and people around the world. There are many, many different diseases that fall under that category of autoimmune diseases, but they all involve the immune system deciding to pick on one or other part of our own body as if it was a foreign infection and damage it. Type 1 diabetes is an example where the immune system picks on the cells that make insulin. Rheumatoid arthritis, about one percent of people have that – the immune system decides to damage the joints. Many others like that: systemic lupus, where the immune system decides that our own DNA is foreign and starts to attack it all over the body.

So these are terrible diseases for people that are affected by them. Thankfully 95 per cent of people are not affected by them and really what my research is trying to do is to figure out, well, what’s gone wrong in the five per cent who do have one or other kind of autoimmune disease, how can we fix that, and what can we learn from the other 95 per cent where we’ve managed to avoid setting off our immune system against the wrong targets.

Interviewer: And that’s the people who suffer from arthritis or diabetes and have in some cases quite unpleasant lives unfortunately.

Prof Goodnow: Very unpleasant. And the trouble is that at the moment for most people that are in that situation we can only treat the symptoms and not the cause, and some autoimmune diseases are rising at quite alarming frequency. Type 1 diabetes for example is doubling in its incidence about every ten years for reasons that we really don’t know. We assume something’s changed about our lifestyle or our environment or diet that’s working in concert with our intrinsic genetic make-up, and it’s those kinds of things that our research is trying to really shed light on.

Interviewer: Now, with the Australia Fellowship you’ve obviously now got time and money to do the type of work that you want to do. Where do you see the Fellowship taking you?

Prof Goodnow: For me this comes at a very exciting time in my career. Up until now I guess you know the problem, the core problem, has been very much this problem: how does the immune system tell the difference between friend and foe? And we’ve depended very much on laboratory mice to essentially be the equivalent of a mechanic and get under the bonnet and see how the engine works, what the wiring and circuits are. We’ve had tremendous success in that. We’ve been able to define mechanisms that the system is way more intricate and elaborate than we ever could have imagined in terms of the types of things that the cells do and the programs and circuits that guide those cells.

We’re now at a point where we have a fair degree of precision in understanding those circuits – we still have a long way to go – but enough information that we can actually go back to people, armed with the information about those circuits, and see in someone that does have an autoimmune disease what’s different about the way the immune system circuits are running in that person compared to someone who avoided autoimmune disease.

Of course those circuits in our body are written in DNA – they’re our genes – and it’s only now that in the last couple of years that the tools have become sufficiently powerful to sequence our genes en masse that we could actually go and look at a group of people who have an autoimmune disease, and a group of people who have avoided it, and get a list of all of the differences in all of their genetic circuitry. And then based on all the other information that we’ve been amassing over the last 20 years, what we hope is that we’ll have some eureka moments, that we’ll say: “ah circuit number 328 has a broken connection”. And we know about circuit 328 because we’ve been working on it in mice for the last three years and there’s publications around the world.

So that’s what the Australia Fellowship, if we’re as successful as I hope we will be, will allow us to finally do. We couldn’t have even contemplated doing it five years ago because the tools weren’t there, and even if the tools had been there ten years ago, we wouldn’t have been conceptually ready yet because we didn’t have enough information about the circuitry.

Interviewer: So everything’s coming together at this point to just be the right combination?

Prof Goodnow: That’s right.

Interviewer: So you’re obviously talking about working with a team. Now working with that team you’re also building the potential for capacity for medical research in Australia?

Prof Goodnow: That’s right and one of the other things that’s exciting about this is that the members of that team come from a really broad range of backgrounds, and many of them actually straddle the clinical and the laboratory side. So we have people who are card-carrying clinical immunologists, who have also got PhDs in basic immunology, people who are just finishing their science degree and are learning from their clinician colleagues about what’s really important in the clinic. And there are people who are coming from hard-core molecular biology or bioinformatics, computer science, genetics. The idea is to make sure that every member of the team can speak each other’s language and ideally is conversant in the whole system if you like, from the clinic to the laboratory bench.

And we think that will create the essential capacity that we’re absolutely going to need in the clinic of the future, because there’s absolutely no question that one of the key tools that we’ll always use in medicine going forward will be a DNA fingerprint. So I’m hoping that what we’ll be doing through the course of this is also training people in how to use these kinds of tools as an additional and very powerful part of the clinical diagnostic worker.

Interviewer: Professor Goodnow, thank you very much for speaking to us today.

Prof Goodnow: It’s a pleasure.

Voice-over: This podcast was brought to you by the National Health and Medical Research Council, working to build a healthy Australia. You’ll find more information about this and other health and medical research issues on our website at www.nhmrc.gov.au.

Page reviewed: 8 April, 2011