Helen Poska: “Motivation alone is not always enough”

How did you come up with this topic during your studies?

I would have to say that my job played a role, along with a little bit of luck and chance. During my Master’s studies, another student asked me to substitute for them in the cell work lab while they were away on holiday. From there, things got really interesting, and a little while later, I took on a more meaningful role in the project. So, I happened to be in the right place at the right time. And then, immediately after graduation, Sandra Zetterström Fernaeus, my supervisor at the time, offered me a doctoral thesis topic. As the theses from my previous levels had been thematically and methodologically very different, I guess all I really needed was the little push I got from taking part in the project. So, I am very glad that despite my previous little knowledge and experience, people saw some potential in me.

Writing a doctoral thesis is a huge task and definitely needs constant self-motivation. What’s your trick? How were you able to consistently work on it to achieve a successful final result?

Some things you just have to do; motivation alone is not always enough. I think consistency is the key – it helps keep everything in focus. This applies to the writing process as well as the necessary research, reading and experiments. In my opinion, if you are constantly engaged and not taking it as a mere Sunday project, then everything becomes much easier and the motivation will come. Another important aspect is continuous and open communication with your supervisors and others involved – in my case, people inside and outside the lab. You should also not forget to take time off to relax.

Please describe a memorable or funny event that happened while you were writing your thesis.

I remember a situation where, right before I had to present my work for the first time and confirm my final topic with my supervisor, I had to shamefully admit: “I have lost the title”.
 
Both the focus and the topic changed throughout the writing process, so before submitting the dissertation, I still had to change the official title and get my supervisor’s approval. We discussed this thoroughly, then finally managed to articulate a new title and confirm it in writing via e-mail. But a day later, when I started putting together the e-mail to confirm the title with the university, I discovered, I had hopelessly lost all the e-mails I had exchanged with my supervisor alongside every paper trail I thought I had left of the final topic. Finally, we managed to find the title from the supervisor’s inbox, so the theses were not left untitled.
 
I actually wrote my dissertation in Sweden at the Karolinska Institute under the supervision of Jan Johansson. Another memorable moment happened during my preliminary defence. At the exact time I was presenting my work, the fire alarm started. So, while my opponents and colleagues from the alma mater in Tallinn were on Zoom ready for the preliminary defence, my supervisor and I were waiting outside with everyone else for the firefighters to arrive. What a thrill. That time, however, it was not just a badly timed drill; in the lab next to ours, a real fire had broken out that needed to be extinguished. In the end, everything worked out fine: the paper got a title and the preliminary defence was successfully completed, with a 15-minute delay.

How is your research going to change the world?

It will most likely not change the world, but I can dream. I hope that it will at least provide a direction for some kind of change (for the better). The majority of my research is closely connected to a domain located in proteins – the BRICHOS domain. One of its functions is considered to functionally bind proteins and to make sure they are not bound incorrectly. For proteins to be able to do their assigned jobs in the organism, they have to reach their functional conformation, which means that they have to be bound together in the right way. If proteins are not bound in the right way, they clump together or aggregate. Protein aggregation is the cause of a number of illnesses, Alzheimer’s disease, for example. In general terms, proteins from two types of aggregate (accumulated and mostly toxic clumps of proteins that do not have the same primary function in the body as the protein would) under the influence of certain stressors: the very structured amyloid fibrils and the irregular amorphous aggregates.
 
We succeeded in demonstrating that the BRICHOS domain works on Drosophila melanogaster (fruit flies) and substantially reduces the deposition of peptide Aβ42, which is closely connected to Alzheimer’s disease, and also regulates the changes induced by its toxicity. Furthermore, we were the first to prove that different BRICHOS domains can slow down the different types of aggregation of proteins – both amorphous aggregates and amyloid fibrils. Our study also showed that the BRICHOS domain is a molecular chaperone that enables the inheritance of the more common amorphous aggregation, and we found the region in the BRICHOS domain potentially responsible for this.
 
Although, at the moment, this is not knowledge that could change the world, it does provide a basis for further research so that in the future, with the help of this domain, we could develop a cure for the illnesses connected to the aggregation of proteins.

How much are the voices of scientists and young researchers heard in our society?

You can hear them really well if you just listen.

What are the most important values and beliefs that you live by?

If we are strictly speaking about doctoral theses and the writing process, I would say: “Little by little and bit by bit”.