Advent calendar - December 1st - Sajitha Sasidharan

In the Zernike Institute Advent Calendar, we are presenting 24 short spotlights in December. In these specials, we highlight PhD students, postdocs, support staff and technicians of our research groups and team - providing a glimpse in their typical day at work. In Episode 1 meet Sajitha Sasidharan, Marie Curie post-doctoral researcher in the Molecular Biophysics group of Prof. Wouter Roos .

Working with the stimulus-responsive materials during my doctoral research, I was fascinated about how cells constantly sense, respond and adapt to their physical environment. I joined as an oLife (origin of life) Marie Curie post-doctoral researcher in the Molecular Biophysics group of Prof. Wouter Roos to explore the role of mechanical forces as a driving factor in shaping cellular evolution. I worked with these tiny packets of messengers called extracellular vesicles (EVs). These tiny entities released by the cells deliver vital cargo and dispose of wastes to keep the cells running. The interesting part is, irrespective of the organism or their cell type, the release of EVs is a universal mechanism conserved through evolution. It beats all the odds to connect even the simplest microbes to complex organisms.

I am interested in the role of the small EVs, especially their physical properties in shaping the cells. Considering their tiny size in nm and sensitivity to the working conditions, we used an Atomic Force Microscopy-based indentation approach. We apply small forces in terms of picoNewton and nanoNewton. Applying a force with a tiny tip of ~15 nm reveals the softness or stiffness of the EVs with precision at the nanoscale. The information obtained beyond its evolutionary standpoint has pathological implications. As the EVs carry the signature of their parent cells, they help backtrack their nature, which is crucial in differentiating normal cells from the diseased state. In my research, I could explore the mechanical properties of the vesicles from cancer cells, namely HeLa and SiHa, under different oxygen conditions and I explored the properties of synthetic systems such as liposomes and polymersomes targeted for drug delivery and building a synthetic cell.

The privilege of working with samples from collaborators within the Netherlands and across Europe gave me an opportunity to collaborate with research groups, answering different scientific questions. Through the EU-funded oLife programme, I gained insights across various disciplines, contributing to understanding the origin of life. I also had the rewarding opportunity to supervise some brilliant and hard-working students.

My typical days: When I am performing experiments, I am in the Atomic Force Microscopy (AFM) room straight for a week as my sample comes with limited validity as it will start degrading afterwards. Otherwise, I am mostly in front of the computer, analysing data. One of the most challenging parts is finding the right substrate to stick the vesicles well enough for the indentation experiments, but not so much that they end up forming a pancake. But the best part is visualising the 3D structures of these tiny entities. The windowless AFM room is where I find my solace during winters and when the experiments are running smoothly; as Einsteins quoted, “Time is an illusion”; you feel that you've only been there for minutes when it’s actually been hours.

The best part about the Molecular Biophysics research group is it is very interdisciplinary and international. During group meetings, you are bombarded with questions and fresh perspectives. Outside work, they are a bunch of cool people (bookworms, sporty, philosophical and foodie), I enjoy spending time with. Being with the group, I learned so many beautiful and interesting things about different cultures. But I haven't figured out one thing yet...The right way to eat a Tompouce...