‘We’re trying to target different parts of the cell’

Philip Gale and his research colleagues are working on chemistry fundamentals which could pave the way for the molecular-level treatment of diseases such as cancer and cystic fibrosis. Molecules can be seen as little machines that perform a certain function, he says, and understanding how these tiny “machines” operate and interact provides an essential foundation of knowledge for further research into a variety of crippling diseases.

“We’re very much at the fundamental end of this,” he says. “We’re designing molecules and looking at how they transport anions like chloride: fundamental foundations that may in the future be useful.”

Cystic fibrosis, for example, is caused by a genetic problem with chloride channels in the cell membranes in the lungs which prevents chloride from crossing the cell membrane, he says. Gale’s research group, along with others, is working on the idea of replacing the function of the faulty chloride channel with a small molecule which would allow chloride to move through the cell membrane into the lungs, which may ameliorate the debilitating illness’s symptoms.

Now deputy dean of science at the University of Technology, Sydney, Gale first came to grips with supramolecular chemistry at Oxford University, in his fourth year of a chemistry degree, a year specifically devoted to research. Originally from Liverpool in England, where he went to a comprehensive high school, he continued his Oxford research in the field for a further three years and completed his doctoral degree in chemistry at the university.

From the time of his first forays into molecular chemistry, Gale was interested in anions – negatively charged ions, rather than the positively-charged cations that were then absorbing the interest of many other chemistry researchers.

As a Fulbright post-doctoral scholar at the University of Texas in Austin, he expanded his research into anions. “Over the years my work has gone from just making receptors for things that are negatively charged through to making compounds that can transport them through cell membranes,” he says, adding that it can be difficult to get something that is charged through these membranes. “What we’re trying to do is make molecules that will bind to chloride and wrap it up in an oily coat and then allow that molecule chloride complex to diffuse across a cell membrane.”

Changing the concentration of anions and cations in cells could also trigger cell death, and might be potentially be a new approach to treating cancer, Gale says. He and his colleagues are trying to make compounds that switch on under the chemical conditions found in a tumour, which should be different to the conditions found in healthy tissue. “We’re trying to target our transporters to different parts of the cell; different sub-cellular compartments do different things,” he says. “We’re trying to target the different parts of the cell to see what happens.”

Gale devotes about a fifth of his time to research to keep his research group going. The rest of his effort is absorbed by administrative duties. “I’m one of those strange academics who actually like being in administrative roles,” he says. “It’s eaten into the time I have available to do research, but I’ve been very fortunate to work with really talented people in my research group.”

The Australian