Some of his work is behind him

Another relic from ye olde archives, I'm including this one because it gives a glimpse into how I spent a year of my life. 2006: The Year of the Honours!

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Cure cancer? Sure can, sir!

“…which may lead to a cure for cancer.” If I had a dollar for every time I’ve heard these words, I’d have enough money to fund research which may lead to a cure for cancer.

The hopeful tone of media reports is indicative of the enormous problem cancer poses to society. First and foremost it is a profoundly personal issue, but these days you’re also likely to see it framed in economic terms — lost hours (and years) of productivity, the burden on the healthcare system. Whichever way you slice it, one result has been considerable investment into cancer research.

Thousands of torches have been flung into cancer’s dark caves. As more space is lit up, more caves are revealed, typically connected to the cavernous depths of other areas of biology such as the cell cycle, genetics and the immune system. What will be the outcome of this oncological spelunking? Will we cure cancer and if so, what are the implications for society? We will come to these questions in due course, but it behoves me to first explain my role in all of this.

The link between the cytoskeletal protein tropomyosin and cancer is not obvious, but I hope to change this. The cytoskeleton is an extraordinary system of filaments and regulatory proteins tied up in a huge range of processes, including mitosis and muscle contraction. I study the cytoskeleton in neurons, which are great for this purpose because of their unique shape and easily identifiable compartments.

The cytoskeleton hasn’t always been appreciated. In my school days I was taught that the cell was a watery sac through which the molecules of life whizzed and spun. The cytoskeleton, if mentioned at all, was merely cellular scaffolding, a backdrop to more important events. This picture has changed dramatically. Today a more appropriate mental image is of responsive, rapidly remodelling networks and vast cellular superhighways, complete with exits and accidents.

We have known for some time that cancer cells possess an altered cytoskeleton. This may help them leave their site of origin and invade other tissues — a most malignant act. As a major component of the cytoskeleton, actin has been considered a logical target for chemotherapy. The problem is that all attempts to develop a viable anti-actin drug have been stifled by actin’s involvement in more biological processes than you can poke a filament at, including the life-sustaining contractile machinery of the heart and diaphragm.

This is where tropomyosin comes in. Most actin filaments in the body are not naked, but adorned with tropomyosin, itself a filament. Recent research suggests that tropomyosin is well placed to regulate the actin cytoskeleton throughout the whole body[1].

Thanks to the molecular card shuffling that is alternative splicing, there are over 40 different versions, or isoforms of tropomyosin! Different tropomyosin isoforms reside in different cellular locales, and appear able to regulate the access of a litany of other proteins to the all-important actin filament. A diminutive doorman, if you will. Perhaps most significantly, different actin filaments are decorated with different tropomyosin isoforms.

The upshot of this is that we could disrupt specific (non-essential) populations of actin by directing chemotherapeutics against the tropomyosin isoforms which clothe them, rather than actin itself. Right now, more needs to be learnt about the localisation and function of different tropomyosin isoforms, which is how I busy myself. The ultimate goal of my research is an effective cancer treatment and a greater understanding of the cytoskeleton.

But what about preventing cancer, rendering treatment unnecessary? Might we upregulate DNA-repair enzymes, reducing mutation and with it the grist for evolution’s mill? Perhaps then we could truly say goodbye to cancer as a life-threatening condition. Before popping our champagne corks, we would do well to remember that as (currently) mortal beings inextricably connected to our environment, the war against illness and disease is perpetually waged but never won.

Before wading into the opaque waters of philosophy, I will end in a fashion increasingly required of scientists; a practical one. It is simply our duty to do what we can to reduce extremes of pain and suffering in our fellow human beings. And that is what I’m trying to do.

[1] Gunning, P. W., et al. (2005). Tropomyosin isoforms: divining rods for actin cytoskeleton function. Trends Cell Biol 15(6): 333-41.