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Professor James Whisstock

Young, groundbreaking and inspiring

6 June 2008

Professor James Whisstock

When is being wrong a good thing? What role do enzymes play in human disease? What do genes and computers have in common?

Professor James Whisstock is the multi-award-winning research head of Monash University’s Department of Biochemistry and Molecular Engineering, and an inspiration to countless PhD students who have gone on to win awards in their own right.

Here he talks about his own groundbreaking discoveries, what inspires him to be a medical researcher and what happens when the knowledge era meets biology.

This podcast was recorded the night James won the prestigious Commonwealth Health Minister’s Award for Health and Medical Research, which was sponsored by the NHMRC.

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Transcript of podcast

Voice-over: Welcome to the 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: Hi I’m Dr Andi, I’m at the Australian Society of Medical Research dinner. I’d like to introduce you to Professor James Whisstock from Monash University Department of Biochemistry and Molecular Engineering. James, congratulations on winning the 2008 Commonwealth Health Minister’s Award for Excellence in Health and Medical Research.

Prof. Whisstock: Thank you very much.

Interviewer: Now in order to find out what exactly you do as a medical researcher I’m going to ask you some tricky questions.

Prof. Whisstock: Right.

Interviewer: First of all what is your favourite internal body organ?

Prof. Whisstock: Well I reckon the liver’s a pretty special organ.

Interviewer: Why?

Prof. Whisstock: Well basically if we didn’t have a liver then we wouldn’t be able to enjoy wine or beer, so on and so forth, and I must admit to liking a pint occasionally, but also the brain.

Interviewer: So the liver and the brain are your favourite organs. Is there a particular reason that they’re your favourites? Do you work on them?

Prof. Whisstock: I work on aspects of their function so basically in regards to the brain we do a lot of work on a protein called glutamate decarboxylase, which is the enzyme which produces something called GABA[1]. GABA is an inhibitory neurotransmitter and if GABA levels are perturbed this can result in pretty horrendous diseases, parkinsonian-like diseases, schizophrenia, depression, movement disorders and so on and so forth, so we’re very interested in understanding how GAD[2] works and how it controls such activities within the brain.

Interviewer: So GAD would have to be one of your favourite enzymes and molecules, have you got another one?

Prof. Whisstock: Absolutely, the serpin super family is what I did my PhD on and I think that when you do something like a PhD, as you know, it’s a pretty long and horrendous drawn out process and the protein family I worked on was serpins. These are molecules which control proteases. Proteases are proteins which break down other proteins and the serpins areif you like are the controllers to make sure the proteases don’t go and break down too many other proteins. They control processes such as blood clotting, which is obviously really rather important.

Interviewer:  When I looked at the types of things that your work applies to the list was endless. It’s viral infections, liver cirrhosis, it’s thrombosis. Is there biochemical connections to all of these types of conditions?

Prof. Whisstock: I think science takes you in lots of directions that you don’t necessarily expect, and so things just sort of sometimes happen, and you start working on one area and suddenly you get taken to somewhere else. And I think it’s really important not to say well, this doesn’t fall into my little basket of what I’m supposed to work on, you just follow where it takes you and follow where the science leads.

Interviewer: Now you’re a multi-award winner, your office must be full of certificates and plaques and trophies...

Prof. Whisstock: It’s actually full of paper.

Interviewer: Is it? I can imagine, but somewhere in the corner you’ve had the prestigious 2006 Science Minister’s Prize for a Live Scientist, you’ve been Victorian Young [Tall] Poppy Award Winner, so you’ve got a whole list of prizes. It sounds like you’ve had success and success and success, but do you ever have a really bad day or perhaps a bad couple of months where you’re going up a garden path and things aren’t working, but you need to redirect your research somehow?

Prof. Whisstock: Of course I have bad days at work, everyone has bad days at work. You raise a very interesting issue there. It’s important to remember that science is about knocking down your ideas, and a lot of people think it’s about just proving things. You can’t prove really anything in biochemistry. You can support hypotheses and the way you do that is by trying to disprove them. That can actually be a very disheartening process because a lot of the time we’re wrong and there’s no shame in being wrong, it’s really important to be wrong, because I think Einstein said ‘now I know better than I did before’ and it’s very, very true and basically that can be dispiriting because you get a lovely model, a lovely idea about how something works, it all looks great, you do the critical experiment and then you go Oh, never mind, let’s think again!

Interviewer: Pod listener, you have the pleasure of listening to Professor James Whisstock, he’s a Monash University scientist, he’s in the department of Biochemistry and Molecular Biology. He’s also this year’s 2008 Commonwealth Health Minister’s Award for Excellence and that’s sponsored by the National Health and Medical Research Council. Now James tell us about what inspired you to become a medical researcher. What were the influences that said Yes, this is an interesting way to work?

Prof. Whisstock: I think that science in itself — what I work on is protein structure and how proteins I guess operate and how they function, and proteins are like little machines and, you know when I was a little boy I guess, I loved like kind of taking things apart and putting them back together, generally pretty badly and essentially breaking things and my long suffering father would then try to fix them. I think that personally from my perspective I love doing what I’m doing because basically it’s essentially trying to understand how things work. It’s also obviously I think as you grow and develop as a scientist suddenly you start thinking Ooh, actually this could be quite useful.

I think most scientists probably start off being very ‘blue sky’ and basically — I don’t care I’m just interested in this problem, I want to address it. And then as you sort of grow older you suddenly think well this could be useful to improve the human condition or to improve human health and obviously health is something that affects us all, affects everybody and being ill is pretty rotten. So I hope that some of the work that we do eventually will result in approaches to treat certain diseases.

Interviewer: Sure. Making a difference which you certainly are. Tell us about where your research might end up. I know it’s something you can’t plan — as you say, you never quite know what’s coming up next — but where do you hope it will end up?

Prof. Whisstock: I work on a lot of different things. I think that I would be delighted if the goal of really what I’d love is for example to develop a therapeutic which improves people who have mental illness or have movement disorders and so on and so forth. That’s one example. But the point I’d like to make is that it’s very difficult to predict where you’re going to go. Obviously it’s useful to think about it, it’s important to think about it, and we do our best to translate the discoveries that we make into useful biotechnological and/or medical advances, but I think if you try to predict too hard then you can actually limit where you go.

Interviewer: I know that you teach structural biology and bio-infomatics, just tell us about bio-infomatics for those that aren’t up to speed with what that is.

Prof. Whisstock: Okay, well bio-infomatics is the study, computational study, of genome sequences. For example the human genome which was an amazing project which basically suddenly really revolutionised and opened up our ability to understand what makes us tick. The trouble is there’s a huge amount of information there and actually one of the interesting things is the revolution in genome sequencing has actually very closely followed Moore’s law, which is of course the acceleration in computational power. And it’s not a coincidence, i.e. computational biology is absolutely key for dealing with the vast amounts of data. Imagine for example if I gave you a stack of a hundred yellow pages and I asked you to rip them all up and put them in a big bin and then I asked you to put it all back together again. You’d be spending a very long time gluing bits of paper back together. If you had a computer to help you do it you’d probably be able to assemble things very fast. So that’s the type of I guess infomatic direction that I address.

Interviewer: So it’s where the knowledge era meets biology?

Prof Whisstock: I think so. I think that’s a good way of putting it. When I started my PhD in 1992 I had on a desk a huge box, which was basically a silicon graphics IRX computer, which basically now a pocket calculator would probably be able to kind of dwarf in terms of power. I’m not that old or I don’t reckon I’m that old. I’m 36 and what’s happened in the last 15 years in terms of computers is just astonishing, absolutely astonishing, and I think that every generation probably sits there and has one thing which they look at and go My gosh, hasn’t that changed. The other thing which has changed the way we do science is the World Wide Web, because basically the ability to pull down sequences of genomes pretty much instantaneously from databases which sit on servers in the US and so on and so forth again is very, very powerful and very important.

So our ability to communicate, our ability to share data and our ability to deal that information has really moved biology into sort of the big systems biology era.

Interviewer: Professor James Whisstock you’re an absolute gem. It’s been a delight to meet you. Thank you for talking to us.

Prof. Whisstock: Thank you very much.

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.

Footnotes
  1. GABA: gamma-aminobutyric acid [back]
  2. GAD: glutamate decarboxylase [back]
Page reviewed: 8 April, 2011