NL
DE
As scientists, we love to share our success stories. An interesting discovery, a big grant, or a prestigious prize is the perfect reason for a post on social media or a newsletter message. However, doing research also means dealing with failed experiments, rejected grant applications and broken equipment. In this series of Untold Stories in Science, junior editor and PhD candidate Laura Akkerman wants to discover the struggles that scientists face in their day-to-day work. What does not go according to plan, and how to deal with it? To kick off the series, she spoke to Cas Boshoven, whose PhD trajectory was a long and sometimes challenging fight with the malaria parasite.
Cas started his PhD with a clear goal: studying transporter proteins of the malaria parasite, which enable nutrients to go from one cellular compartment to the other. ‘You can compare a transporter to a gate, like on the cover of my thesis, which only allows specific substances to pass. For example, the malaria parasite needs a sugar transporter and a vitamin C transporter to obtain these nutrients.’ The plan was simple: make a list of interesting transporters with an unknown function, and investigate them with many different molecular tools. More than five years later, on October 29th, Cas will defend his thesis, which describes all the work he did to study these transporters. Quick summary: still, none of the functions are known. But what happened in between?
Cas’s thesis cover, with the gate that represents the transporter proteins that he studied.
Challenged from the start
The struggles literally started when Cas began his research project, in March 2020. Within a month, the country was in lockdown to prevent the spread of the COVID-19. Trainings on crucial equipment were not possible, orders of lab stuff suddenly took months instead of days to arrive, and lab time was limited. Once the lab got back up and running, technical problems started to arise. The genetic modification of parasites, which was an essential tool for Cas, did not work for months. Instead of spending time on studying interesting proteins, Cas was stuck troubleshooting the methods that he needed. ‘There is a big difference between having negative results and no results. With negative results, you asked a question and didn’t get the answer you were expecting. With no results, you have no informative answer to begin with, and it feels like you are completely stuck.’
After a long period of ‘no results’, the endless troubleshooting started to pay off and the first actual discoveries were made. Excitingly, one transporter showed a peculiar localization, hinting towards a previously undiscovered function. Soon however, a new challenge arose: conflicting results. Using a slightly different approach, Cas wanted to confirm his findings, but unexpectedly, the outcomes were completely different. Eventually, Cas solved the mystery, but another year of precious research time was lost. ‘We all know that struggles and drawbacks are part of research, but at some point you start doubting everything, including yourself. But my PhD was so much more than just science. I supervised students, co-organized a master course, made science communication videos, and attended a conference at a beach town in Australia. It also helps if your colleagues become your friends (and wife).’
New lab, new chance?
In the summer of 2023, the tide seemed to turn. Cas obtained a grant to visit Professor Edmund Kunji’s laboratory in Cambridge, which has a well-established pipeline to study transporters. The general belief was that if a transporter can be produced in this system, its transported nutrient can be found. ‘Looking back, I really thought that the grass would be greener on the other side’, Cas reflects on his time in Cambridge. ‘Initially, when I managed to produce the transporter protein, I was thrilled that we might actually get somewhere. But this time, biology was not on our side. After screening numerous nutrients, we didn’t find the one binding to my transport protein. An example of actual negative data. But also here, there luckily is so much more than just science. The UK turns out to be a beautiful country to which I would really recommend more people to go on holiday’.
The combination of technical difficulties, conflicting data, and circumstances such as the COVID-19 pandemic have severely affected Cas’s PhD. ‘After all this work, my thesis unfortunately does not contain a published first-author paper that puts one of the pieces of the molecular puzzle in the right place. Still, I came to work nearly every day with a smile. Finishing a thesis is a craft on its own, though. I have never felt so lonely and the only good thing is that it is actually almost completed.’ Then Cas adds smiling: ‘And I still obtained a postdoctoral position at the “excellent University of Cambridge”.’ To summarize with some words from Cas’s thesis: ‘I wouldn’t describe the entire journey as fully satisfying, but still, I am incredibly thankful. It's only in hindsight that you see the breadth of experiences, challenges, and personal development.’
Which challenges have you encountered during your research? Share your story with Laura (laura.akkerman@radboudumc.nl) to get featured in this blog series!
Cas Boshoven explores his temporary home country during a research visit to the UK.
