We are delighted to announce that Sadie Vermeiren, 24, has been selected by an international jury of Parkinson’s researchers as the second recipient of the Demoucelle Parkinson Charity’s annual prize for the best masters thesis by a young Belgian scientist addressing any aspect of Parkinson’s disease – diagnosis, impact, care, treatment or cure.
Along with other candidates from across Belgium, Ms. Vermeiren submitted her thesis together with a short summary and was then shortlisted to present her work to the jury in a second round of adjudication.
Congratulations Sadie!
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Please could you introduce yourself?
My name is Sadie, I’m 24 years old and I live in Brussels. I recently completed my Master’s degree in bio-engineering sciences: cell- and gene biotechnology at the Vrije Universiteit Brussel (VUB). I carried out my Master’s thesis research in the lab of Prof. Wim Versées within the research group Structural Biology Brussels and the VIB-VUB Center for Structural Biology, where I will also continue my career as a researcher.
In my free time, I enjoy contemporary dance and aerial hoop, and I love to travel and hike whenever I can.
Please could you describe your Masters thesis.
During my Master’s thesis, I investigated the function of a protein called DNAJC13. Mutations in the gene (PARK21) that encodes this protein lead to its malfunctioning, and are associated with the onset of Parkinson’s disease. In the cells of the brain, the DNAJC13 protein plays a key role in the degradation, the recycling and the transport of proteins between different compartments of the cells: a process also called “endosomal trafficking”. To perform this function, DNAJC13 needs to bind to the lipid layers, called membranes, that surround these different cell compartments. My research hence specifically focused on this lipid-binding activity of DNAJC13, via three of its regions called its N-terminal pleckstrin homology domains – or “PH domains” in short. In this way I aimed to uncover the mechanisms that target DNAJC13 to specific membrane compartments, and how these mechanisms may be altered in disease.
Very practically, I first needed to find procedures to produce the full-length DNAJC13 protein in a pure form for further studies, as well as each of its individual PH domains. Subsequently, two methods needed to be optimized to enable us to investigate the binding of these proteins to specific membrane lipids called phosphoinositides. Using these methods, I found that the full-length protein exhibited the strongest affinity for a phosphoinositide called “PI(3)P”, which is a characteristic phosphoinositide for the early endosomes in the cell. Additionally, among the three PH domains, the first domain (PH1) appeared to be the major contributor for PI(3)P binding. We were also surprised to find that the full-length protein displayed higher affinity for PI(3)P than the isolated PH1 domain, suggesting that additional elements of the full-length protein could play a role in binding efficiency.
Overall, our results support a model in which lipid binding and membrane recruitment of DNAJC13 are tightly regulated processes that may be disrupted by disease-associated mutations.
How has your research contributed to our understanding of Parkinson’s Disease?
While current therapies can help relieve symptoms of Parkinson’s disease, there is still no cure or treatment that can halt or slow down disease progression. One of the major challenges in developing such disease-modifying therapies is the complexity of the mechanisms underlying PD. In certain cases, the development of the disease can be linked to mutations in a limited set of so-called PARK genes. Many of these PARK genes encode proteins that play an important role in protein degradation, recycling and transport, suggesting that these might be important pathways for future drug design. DNAJC13 is a large and complex multi-tasking protein involved in exactly those processes. Understanding how DNAJC13 is targeted to specific membrane compartments is therefore essential for uncovering its crucial role in the brain. By characterizing the lipid-binding properties of DNAJC13 and its PH domains, my research provides important insights into how disease-associated mutations in DNAJC13 may disrupt these pathways and consequently contribute to neurodegeneration. This work helps lay the foundation for a deeper understanding of PD mechanisms, which is essential for the development of future disease-modifying therapies.
Why did you decide to research Parkinson’s disease for your Masters thesis?
Parkinson’s disease is a devastating disease that affects millions of people worldwide, while there is still no real cure for the disease. Contributing to our general understanding of the very complex mechanisms that underlie this disease is thus not only a scientifically and intellectually very challenging topic, but also has a real societal importance. During my studies, I became especially interested in understanding the very detailed mechanistic aspects of neurological diseases, for which structural biology is a perfectly suited methodology. Finally, I was also drawn to this project because of the lab where this research was performed: the people and the collaborative atmosphere made it an exciting place to carry out my research.
Have you had any personal experience with Parkinson’s patients and what impact has that had on you?
Apart from the scientific and societal reasons to perform research in the field of Parkinson’s disease, there is indeed also a more personal motivation. Unfortunately, my grandmother on my father’s side passed away from Parkinson’s disease, although I never had the chance to know her personally.
What does it mean to you to receive this prize and what are your next steps/plans for the future?
I am truly grateful to be selected as the winner of this year’s thesis prize. Presenting my work and having the possibility to discuss my results with experts in the field was a great opportunity and a very rewarding experience. The price also genuinely feels like an extra recognition for the hard work I put into my thesis.
Looking ahead, my plans are to continue to perform research into the detailed mechanisms underlying neurological diseases in the Versées lab, but this time focusing on a different protein implicated in the same types of pathways. I’m excited to keep building on what I’ve learned and to contribute in a meaningful way to advancing our understanding of these devastating diseases.
And finally, what is your favourite quote or piece of life advice?
My life advice would be to stay curious, to be open for new experiences and to not be afraid of stepping outside of your comfort zone.