First person – Darshika Tomer

Darshika Tomer

How would you explain the main findings of your paper in lay terms?

Extracellular matrix (ECM) is the network of proteins outside of cells. Apart from providing structural support, ECM relays signals, for example, those necessary for embryogenesis. Fibronectin (Fn1) is a major component of ECM in different tissues, and it is known to play key roles in cell polarity, cell fate decisions and embryogenesis. Fn1 dimers assemble into extracellular matrix fibrils that appear as long (>10 µm) threads when viewed using conventional fluorescence microscopy. How Fn1 dimers assemble into fibrils that are orders of magnitude larger than Fn1 molecules has long fascinated biologists. We found that fibronectin fibrils are actually periodical arrays of nanodomains, wherein each nanodomain consists of multiple fibronectin dimers. One can think of a fibronectin fibril as a string of pearls in which pearls are spaced at regular intervals. What lies between the pearls and what determines periodicity are among the next key questions.

Were there any specific challenges associated with this project? If so, how did you overcome them?

We have unraveled a novel structural aspect of fibronectin fibrils, and in order to convince ourselves and the field, we had to learn multiple different imaging techniques. Learning how to do super-resolution microscopy properly took a lot of time and effort. We are grateful to all who helped us with these challenges and encouraged us to persevere and push forward with experiments. COVID has been an especially challenging time. On the one hand, the shutdown gave us the time needed to analyze data, but on the other hand, we had to make difficult personal choices that affected our ability to work in the lab.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

When we first observed it, the beaded architecture of Fn1 fibrils was very puzzling. Fn1 fibrils were thought to resemble continuous ropes of extended Fn1 molecules. Seeing seemingly discontinuous arrays of beads when imaging fibrils at a high resolution was contrary to the traditional view of what Fn1 fibrils ought to be. Initially, we spent a lot of time trying to prove ourselves wrong. But every time we tried to dissuade ourselves, we saw the beaded architecture of Fn1 fibrils at different magnifications and resolutions, using different imaging approaches, multiple cell lines and tissues. The ‘eureka’ moment came when we used super-resolution microscopy and polyclonal antibodies to Fn1. Seeing Fn1 fibrils as beaded arrays in this experiment suggested to us that each ‘bead’ of the beaded arrays contained the entire Fn1 molecule. We are very excited about our discovery and believe that our studies will change the view of Fn1 matrix formation and assembly.

Why did you choose Journal of Cell Science for your paper?

Journal of Cell Science publishes beautiful papers in the field of cell biology that we enjoy reading on a regular basis. For our first cell biology paper, we wanted to be a part of this community.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

It is hard to choose one mentor out of many, as I was fortunate enough to be surrounded by great mentors in the form of colleagues, seniors, and friends. I would especially like to acknowledge Dr Sophie Astrof, who accommodated my pregnancy and the pandemic lockdown with the work. Apart from her scientific acumen, I would also like to instill in others her enthusiasm for discovery and ability to infuse fun atmosphere around her.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

I think the world around me motivated me to pursue science. I have always been fascinated with nature and feel a sense of wonderment when I see images from the Mars Rover or a live embryonic heart beating under the microscope. I am always up for a how/why question, and enjoy interacting with scientists from all communities to learn more.

What's next for you?

I am looking for teaching positions right now and writing for grants in order to start working in the lab soon.

Tell us something interesting about yourself that wouldn't be on your CV

I love reading books of all kinds, and I review books as well. I like to go on treks when I find the time. I relax by practicing quilling and making paper portraits.