Scientist Bryony Telford’s cancer research is driven by an inquiring mind.
"I am endlessly curious and love trying to piece together all the little pieces of evidence I have generated with what other people in my lab do and other people in other parts of the world have done," she says.
Given an Otago Daily Times Class Act award while at South Otago High School, Telford now works for a small biotechnology company in The Netherlands characterising miRNA — small RNA (ribonucleic acid) molecules — that are promising candidates for treating cancer.
Although the first miRNA was identified more than 10 years ago, it is only recently that scientists have begun to understand the scope and diversity of the molecules that naturally occur in the genomes of plants and animals. Growing evidence shows they have a range of regulatory functions related to cell growth, development and differentiation.
Telford says they could be used as a biomarker, to predict prognosis and response to drugs, but also in the same way as a drug, getting to the cancer cells and killing them.
"When particular miRNA are lost in cancer cells, the expression of lots of different genes changes, which can give the cancer cell an advantage and help it grow and survive," she explains.
"Our tactic is to reintroduce this miRNA back into the cell to hopefully restore the expression of these genes to their normal levels and stop them from having any survival advantage."
Telford is growing human liver, lung, pancreatic and colon cancer cells in dishes so she can study the effects of miRNA on them. This involves functional studies to see if the cells treated with miRNA are dying or changing in appearance, and gene expression studies to see what particular genes the miRNA is regulating.
MiRNAs are already being used in clinical trials but she is not sure when these types of therapy will be used in standard care. One of the biggest hurdles is they are difficult to deliver to a site where cancer is growing.
"Human blood has all sorts of enzymes that are designed to cut up pieces of DNA and RNA they find floating around in our blood stream. It’s part of our immune response," she says.
"This means we need to package the miRNA inside something to keep it safe, and somehow get that package to the cells to deliver the miRNA where we want it to go. That seems to be one of the biggest challenges at the moment."
Many times she has had to grapple with new techniques and results that don’t make sense.
"At the time it can feel like you’re running up against a brick wall every way you turn. But I’ve always managed to get a bit of perspective, talk to some people who know more than me, and found a way around it."
Telford was not completely sure what she wanted to do when she left high school but knew science was the path she wanted to take. After doing the first-year health sciences course, she was accepted into the physiotherapy programme but decided to carry on with genetics.
"It was about the time that genetic engineering was getting a lot of negative press and I remember thinking that none of the articles I was reading really explained what it actually was. Doing a degree in genetics seemed like a good way to get a better idea."
In her honours year and PhD, she looked at E-cadherin and gastric cancer.
E-cadherin is a protein that helps hold cells together and in some cancers it stops doing this job properly, she says. Some people inherit a mutation in the gene for this protein, which gives them a 60 to 80% chance of developing gastric cancer, often at a very young age. The recommended treatment is to remove the entire stomach, which reduces the risk but has "big consequences for the rest of their life".
The project she worked on was trying to find vulnerabilities in the cells without E-cadherin expression so they could be targeted and destroyed before developing into cancer, without harming normal cells.
This saw her systematically silencing every gene in the genome, one at a time, in cells with and without E-cadherin and measuring which ones caused the cancer-like cells (but not the normal ones) to die. The work was done in Melbourne, which had the robots, reagents and expertise needed for such a large experiment, but continued back in the cancer genetics laboratory at Otago with other students and staff knocking down the most interesting genes to study in more depth: "I was really lucky to work with some awesome researchers, and there are lots of people in the lab still working around this idea."
Her PhD completed, Telford was keen to live and work in Europe. She and her partner flew to Singapore and spent five months cycling around Asia before settling in Utrecht in The Netherlands, partly because it was where the Tour de France started in 2015 and "it looked nice on the coverage".
Cycling is part of everyday life for all ages in The Netherlands so as well as biking to work on an "amazing" network of cycle paths, she and her boyfriend play bike polo and go out with their touring bikes and camping gear at weekends.
The 27-year-old plans to live and work there for a few years, then return to New Zealand and use her skills "closer to home".
Asked about funding for science and technology in New Zealand, she notes some grants have success rates of only 8%: "It means that grant applications have to be quite grand and new, when sometimes it would be better to have some more funding just to really, properly understand some results you already have."
Drug development takes a "really, really long time" and it will be decades before she knows how her research has made a difference. But every piece of information scientists generate, even if it doesn’t seem significant at the time, eventually becomes "part of the story".
"There is a lot going on inside a cancer cell; hundreds of thousands of interactions between different proteins, lots of which aren’t properly understood by scientists yet. So it’s like trying to put an enormous puzzle together when you only have half the pieces," she says.
"Trying to hold all of that information in my head and understand the significance, or where new information slots in, is something I am still practising."
