Kathleen Too talks to Thomas Kodadek about Jacques Cousteau, biomarkers and diagnostic tools.

Tom Kodadek

Thomas Kodadek is based at the University of Texas Southwestern Medical Center where he is professor of internal medicine and molecular biology and also director of the division of translational research. His current research focuses on proteomics and the enzymology and regulation of eukaryotic gene expression. As well as doing basic research, Tom works on the development of protein-detecting microarrays based on synthetic peptides and peptoids. Tom is also the chairman of the Molecular BioSystems editorial board.

 

Who or what inspired you to become a scientist?

I always found the idea of working in an area where I didn't already know the answer to be very attractive. I was influenced by science and nature TV when I was young. In particular, I remember the Jacques Cousteau series, which was terrific but did give one a bit of an odd idea about what scientists do. We don't just sail around the world!

What makes proteomics such a hot area of research?

Post-translational modifications are much more widespread and diverse than people realised. Modifications such as phosphorylation and acetylation have been studied for quite some time. But now we know that there are about 150 common post-translational modifications which are dynamic, diverse and important. People realise that they can't get away with just doing gene chips all the time. So they are interested in new technologies to try to identify and these modifications.

Proteomics also has the potential to have a huge impact on medicine. If you ask clinicians what they think would be the biggest breakthrough, it would be the facile discovery of biomarkers for a particular disease state or a response to a particular drug. They would desperately love to have a simple molecular test to help them design treatment. I think that proteomics is the answer. 

What is the most exciting project you are working on?

We have developed a technology that we think will allow us to monitor immune system responses to almost any disease state. The method uses peptide-like compounds called peptoids spotted onto slides to form an array. When blood serum is reacted with the array, some of the antibodies in the serum bind to peptoids they recognise. These bound antibodies can be detected because they form a unique pattern of spots of light on the array. Because each person has a different combination of antibodies in their serum, they each have a slightly different pattern of spots.

When you get a disease, such as Hepatitis C, the immune system amplifies antibodies associated with the disease. Our aim is to screen a set of people that we know have contracted Hepatitis C. Although the background signature would be different for each patient, each would have a high level of Hepatitis C antibodies and therefore the same spots would be very bright for all the patients. These peptoids would be a biomarker for Hepatitis C. We haven't done that on humans yet; those experiments are ongoing. But we have demonstrated this in animal models.

The first model we looked at was in mice. We have shown that we can give them different sorts of auto immune diseases then use the microarrays to differentiate antibody patterns for those different diseases. The patterns are unique. At least at the animal level, we think we have a generally applicable diagnostic device to monitor disease. Now I hope, of course, that that will translate over to humans but that will be a lot more complicated.

That's definitely one of the coolest things we're doing. It's good to see the clinicians getting really excited about it. That's when you know that you're on to something, when the real doctors want to talk to you.

As the chair of the Molecular BioSystems' editorial board, what have you found exciting in the launch and development of the journal?

I've enjoyed seeing the nuts and bolts of how one tries to launch a journal. In terms of a learning experience, it was eye-opening - there is certainly a lot more to it than simply the science. Scientifically, the most exciting thing is the interaction with the excellent board that we have. They are great people, from a number of different backgrounds, and it's been stimulating to interact with them and hear their ideas about the journal.

Molecular BioSystems has just gone solo. How do you foresee its growth?

We are all going to work very hard to make sure that it's a sound, well-established journal that publishes good articles. It will certainly be a place where scientist will want to publish their work. Our review and highlight content is excellent and we are working towards attracting more and better primary content. The journal will become more successful as the areas covered by it become more active in the UK and Europe, combined with our efforts to reach out to emerging scientists in Asia.

What advice would you give to a young scientist wanting to pursue a career in molecular biology or biochemistry?

Focus on really important problems and differentiate yourself from what everybody else will do. People tend to focus on the same thing, and then it's just a question of who can do their experiments the fastest. That's a bad way to do science. Use your imagination, use your cleverness and give yourself some kind of an edge.

What do you find to be the most rewarding aspect of your career?

Dealing with my students and post-docs. I am very lucky to hang out with really smart people who are engaged and motivated and love to talk about ideas. I have a great group. They do all the real work. I haven't done an experiment in at least five years, so I owe everything to them. They're a lot of fun to work with.

What scientist do you most admire and why?

It would be Linus Pauling simply because the man was a genius. I think that he was the first chemical biologist really. He went all the way from writing what is arguably still the best book on quantum mechanics to discovering the alpha helix. His record is just unbelievable, particularly if you consider his Nobel Peace Prize on top of his scientific accomplishments. Can you imagine if he had gotten the structure of DNA right?