ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Mariana Castro Dias is first author on ‘Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood–brain barrier’, published in JCS. Mariana conducted the research described in this article while a PhD student in Britta Engelhardt's lab at the Theodor Kocher Institute, University of Bern, Switzerland. She is now an Associate Scientific Communications Manager working for Roche Diagnostics International. She is utterly fascinated by the brain, particularly the molecular mechanisms underlying the pathology of neurodegenerative disorders.
Mariana Castro Dias
How would you explain the main findings of your paper in lay terms?
Multiple sclerosis (MS) is a devastating disease that affects the central nervous system, promoting clinical manifestations such as limb weakness or impaired and unsteady gait. Usually, our immune system protects us from external threats, but due to unknown mechanisms, in MS the immune cells circulating in the blood stream manage to infiltrate the brain and attack our own nerve fibers, ultimately causing movement impairment. There are a lot of unanswered questions around this disease, but our work was focused on trying to answer a specific one – how do these immune cells, particularly CD4+ T cells, enter the brain? Previous publications showed that CD4+ cells can move across the blood vessel walls and enter the brain, crossing what we call the blood–brain barrier (BBB). What we found is that these cells specifically migrate across a point where three endothelial cells that compose the BBB meet, which is called a tricellular junction. This is extremely important because knowing exactly how they can access the brain paves the way to a better understanding of the underlying pathology of MS and can be a starting point to try to reverse this process and ultimately stop this ‘self- attack’ on the brain.
Were there any specific challenges associated with this project? If so, how did you overcome them?
To be able to understand exactly how the CD4+ cells interact with the BBB and eventually infiltrate the brain is extremely challenging. Microscopy techniques are fantastic to help us visualize this process and to shed some light on the mechanisms involved in T cell migration into the brain. However, the first challenge was to find a technique that would allow us to specifically investigate the subcellular structures and interactions between the T-cells and the BBB endothelial cells. To be able to do so, we established a fantastic collaboration with Prof. Dr. Benoit Zuber's group (University of Bern), which helped us to identify and establish serial block face scanning electron microscopy (SBF-SEM) as the correct tool to conduct 3D ultrastructural analysis of the migration process. It required a collaboration between scientists with different areas of expertise, a lot of troubleshooting and trial-and-error attempts, but ultimately we were successful, and this allowed us to identify tricellular junctions as a diapedesis pathway in the brain.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
The moment where we used SBF-SEM and observed the interaction between T cells and BBB endothelial cells with such detail was fairly special. However, when SBF-SEM allowed us to observe for the first time that these T cells were migrating across the BBB tricellular junctions was definitely a crucial moment in our study.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
Besides the fantastic supervision I had with Prof. Engelhardt, all the advice, guidance and fruitful discussions I had with Prof. Masuo Kondoh and Dr. Jörg Piontek really made a difference. They were always available for our questions, contributed significantly to move the project further and the collaboration environment was excellent, which is something I truly believe is essential in science.
Primary CD4+ T cell extravasating primary endothelial cell monolayer, captured with serial block face scanning electron microscopy. The light grey highlights the very dynamic shape of the T cell nucleus; cytoplasm and organelles are in dark grey.
What's next for you?
This project was part of my PhD thesis that I concluded in October 2019. Besides loving science, I am also fascinated by scientific communication and the importance of accurately disseminating the valuable information scientists all over the world find every day, not only to the scientific community but also to the lay audience. With that in mind, I have decided to get the best of both worlds and pursue a career in scientific communications and medical affairs in industry. I am currently an Associate Scientific Communications Manager at Roche Diagnostics International, managing communication activities related to Alzheimer's disease.
Tell us something interesting about yourself that wouldn't be on your CV
I did high-level competition swimming for 12 years, while I was still living in Portugal. It took a lot of commitment and many daily hours of practice, but it was such a joy! I just loved it and it really shaped me to be who I am today. Nowadays I still have swimming practice with a fantastic team several times per week, but I don't compete anymore; I do it for the fun of it!
E-mail: [email protected]
