Bench work
Raphaella So is a Croucher scholar currently finishing off her PhD at the University of Toronto. In 2019, Croucher News previously published an article about a paper she wrote when she began her PhD. We caught up with her again recently to talk about her latest research findings and about life as a researcher in Toronto.
So’s latest paper was published very recently in PLOS Pathogens. She explained the background to us: “I have been studying a protein called alpha-synuclein, which clumps together to form aggregates and spreads to different regions in the brains of patients with Parkinson’s disease. As part of my studies, I was looking at the potential of another protein, the cellular prion protein (which was suspected of participating in the spread of alpha-synuclein), as a therapeutic target for Parkinson’s in our mouse model.”
However, So found that the spreading of alpha-synuclein aggregates was largely independent of the presence of the cellular prion protein. This suggests that the cellular prion protein may not be an effective therapeutic target for attenuating the spread of α-synuclein aggregates in Parkinson’s disease.
“This was pretty surprising given that other teams had flagged this as a possibility worth following up,” So told us.
The research came up with another interesting result, though. Mice were injected with the two types of alpha-synuclein aggregates generated in the previous study, S and NS.” Mice inoculated with the NS strain unexpectedly developed two kinds of disease subtypes. Half of them showed the expected NS-like phenotype, but the other half showed a phenotype resembling the faster-progressing S strain, regardless of whether the cellular prion protein was present. One possible reason for this is that as the strain moves from the periphery to the brain, the process of conformational templating—where the structure (conformation) of one protein provides a “template” for neighbouring proteins to fold in the same way—might not perfectly replicate the original structure. This could result in a mutation that creates a new variant that spreads more quickly.
Or it could be that the NS strain might not be a single, uniform structure but rather a collection ("cloud") of different conformations. In either case, says So, “This is definitely worth further study and will be a good project for the next graduate student to join the lab!”
So had to deal with a lot of disruption to her lab schedule early in her PhD because of the pandemic, which limited access to the facilities. However, she still clearly relishes the experimental process. “My day-to-day motivation comes from small findings and the satisfaction of running successful experiments, such as generating aesthetically pleasing results,” she told us. These are often just related to “smaller questions that crop up, filling just a sentence or two in the paper,” she added. At the same time, she also hopes that the work overall will have some positive effect on the world.
“I really like bench work,” she said. “I’ve found that this is what I want to continue to do, either in a company or in a university lab.”
We asked what advice she’d give to her younger self just starting out on her PhD. “If an experiment doesn’t work, just go home, get a rest, and try again tomorrow,” she said. And the second piece of advice she’d give was to find a good distracting activity away from the lab. “I took up dancing a few years ago, and I wish I’d started earlier. It’s great exercise and a good way to relax.”
So has been active in supporting the local community when she has the time—through outreach science communication events and also supporting the work of an old people’s home. Some of the people in the home have Parkinson’s. “Funnily enough, they also use dance in the home to support mobility and social interaction,” she told us.
So misses people from Hong Kong and looks to reconnect when she gets back. She even misses the MTR. “I really like Toronto as a city,” she said. “But the metro system here is not very reliable. It’s sometimes late, and at times it just doesn’t run at all. “It’s great to live in the city centre, though,” she added. “There’s always lots to do.”
Raphaella So’s Croucher profile can be found here.