12 October 2018 – Bladder cancer is the ninth most common cancer worldwide. Dietary factors are likely to play a part in its development, and there is mounting evidence that vitamin A, and its metabolite retinoic acid, can decrease the risk of bladder cancer. However, the mechanism of action is unknown.
Daša Zupančič is an associate professor at the Institute of Cell Biology at the University of Ljubljana, Slovenia, and has been studying bladder cancer for several years, employing a combination of histopathology and light and electron microscopy. Her institute has an excellent track record in microscopy, but Zupančič found that it lacked the capacity for more molecularly-oriented studies. This hampered her ability to get to grips with the molecular mechanisms driving bladder cancer development, including the intriguing link between vitamin A and the disease.
Trading microscopy for molecular biology
Zupančič had wanted to take a sabbatical to learn some molecular biology for a number of years, but life outside of work intervened. She got married and gave birth to four children during and after her PhD. With her youngest child now attending school, and the older three being able to help at home, she revisited the idea of a sabbatical.
One of the most important experimental tools for bladder cancer research is the BBN (N-butyl-N-(4-hydroxybutyl)nitrosamine)-induced mouse model of bladder carcinogenesis, and Zupančič already had a working relationship with the lab of Janoš Terzić, at the University of Split School of Medicine in Croatia, where the model is in routine use. A collaboration looking at the role of vitamin A in BBN-induced carcinogenesis, where Zupančič traded her expertise in microscopy for the Terzić lab’s proficiency in molecular biology seemed a perfect match, and EMBO awarded her a three-month Short Term Fellowship to get the project off the ground.
“I didn’t even know that EMBO existed,” says Zupančič, “but Janoš told me about the Fellowship Programme. I was very happy to find such a great opportunity to apply for money!”
Jelena Korać Prlić, an assistant professor in Terzić’s Laboratory for Cancer Research, gave Zupančič a crash course in RNA purification, cDNA synthesis and PCR, and she set to work preparing and analysing samples from BBN-treated animals fed either a vitamin A-rich, or a control diet. After more than a decade spent teaching undergraduates, with only a little time for research, Zupančič was in heaven: “Having three months’ uninterrupted time in the lab was like travelling back in time and being a PhD student again,” she says. “It was great!” For the first time in years, she also had some free time, which she used to read and to explore Split and its spectacular surroundings with new friends she made in the lab.
Having three months’ uninterrupted time in the lab was like travelling back in time and being a PhD student again. It was great!Daša Zupančič, Associate Professor at the Institute of Cell Biology at the University of Ljubljana, Slovenia
Bringing new ideas back home
Zupančič was impressed by the level of collaboration and equipment-sharing between labs in Split, and hopes to implement something similar back in Ljubljana. “Money is short, and it makes so much more sense to share resources,” she says. She already agreed a deal with another department, whereby the other researchers can use her department’s microscopes in exchange for time on a new scanner for Western blots.
The vitamin A project itself had such promising results, showing that vitamin A clearly hinders the development of urothelial dysplasia in BBN-treated mice, that Zupančič and Korać Prlić are continuing to collaborate. They are in the process of writing up a paper and applying for further funding.
What was the hardest part of Zupančič’s experience? “The most difficult thing was to go,” she recalls. “I felt very guilty leaving the children, but when I saw how well they were dealing with things, I felt OK. In the end, it was a good experience for all of us, and what makes it even better is that they’re still helping out at home!”