For James Matthews, a Victoria University PhD student, his love of biology came from his childhood but took an interesting turn when he entered university.
Working in the new Chemical-Genetics Laboratory at Victoria University in Wellington, Matthews looks at different compounds found in nature to help produce new drugs to fight diseases and conditions such as cancer. "Coming into uni, for some inexplicable reason I got really interested in how drugs were working [and] how [they] were eliciting the response or effects that they do," recalls Matthews.
"It's really expanded the way I think about biology in general because if you want to figure out how a compound does what it's doing you really need to know something about how the biological system is working in the absence of the compound."
Matthews' PhD research focused on a compound thought to be able to kill cells that rapidly divide, like those in cancerous tumours. Found in a relatively common species of marine sponge from the coastal waters of New Zealand, a compound called pateamine was isolated in the late 1980s. Although it was known that the cell had the ability to kill cancerous cells, its molecular interactions were still unknown, which is the key to creating successful drugs.
In order to gather more information, Matthews began running pateamine through different genetic libraries of yeast, an ideal model for genetic testing, to find which deleted genes produced sensitivity to the compound. What the genetic profiles showed was that pateamine prevented the production of new proteins in cells by inhibiting the function of a protein called eIF4A.
To create new proteins in the body is a lengthy process but the first step involves making the protein building blocks, called amino acids. To do this, DNA is changed into a new structure called messenger RNA (mRNA) and is then 'translated' or turned into the appropriate amino acids.
Without help, mRNA strands fold in such a way that prevents them from being translated into amino acids. The eIF4A protein removes the folds in the mRNA strand and allows translation to take place. Therefore, stopping this protein from working means new proteins cannot be synthesised inside cells. Thus, pateamine joined a group of compounds called protein synthesis inhibitors.
"Even though there are a large number of protein synthesis inhibitors known, very few of them have been known to have any sort of selectivity towards cancerous cells like the compound that we're working with seems to," he says. "By comparing our profiles with our compound to other proteins that are inhibitors we may be able to point out the parts of the protein synthesis pathway which are the best ones to try and target if you want to kill a cancer cell."
Though excited about his research, Matthews sees the need for critical thinking as an important tool in a scientists' kit. When asked who the one scientist he would want to meet and work with is, his answer was "unequivocally Francis Crick", a molecular biologist credited with co-discovering the structure of DNA.
"He's one of the only people who have shown an ability to think independent of just the knowledge that he has," says Matthews. "As a PhD student one of the most important things you can do is develop a way of thinking and develop an approach to your science rather than just learning facts and figures. At the end of the day the facts and figures are in a book and I can pick that book up any time, I don't really have to remember them, but its what I do with those facts and figures and how I incorporate them."
