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. Dipanjana Ghosh is first author on ‘ PLP2 drives collective cell migration via ZO-1-mediated cytoskeletal remodeling at the leading edge in human colorectal cancer cells’, published in JCS. Dipanjana is an independent DST Woman Scientist-A researcher at the Indian Institute of Science Education and Research, Bhopal, India, investigating cancer cell metastasis at the proteome-wide level.

Dipanjana Ghosh

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

The majority of cancer patients experience a relapse within few years of surgical removal of the primary tumor. The reason for this is metastasis, which is caused by the ability of the cancer cells to spread from the primary site of origin to a distant location and can take place before the surgical procedure. In our study, we investigated the cellular mechanisms involved when cells spread. In the language of cell biology, we call this cell migration, and this process takes place via balanced, coordinated changes among components of the cell skeleton (cytoskeleton). The whole process is similar to the mechanics involved in the movement of a car. We studied a particular type of migration called collective cell migration (CCM). CCM follows the principle of ‘united we stand’, whereby a group of cells move together by joining ‘hands’, resulting in better success in metastasis. In our study, we report that a candidate protein, proteolipid protein 2 (PLP2), which takes part in driving the movement, acts at the leading edge – or engine – of the moving cell network. We further dissected the detailed mechanisms underlying PLP2-mediated CCM in colorectal cancer.

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

During the project, I came across several experimental, circumstantial and personal challenges. Here I will mention two that I encountered at the experimental level. It was really challenging to create and maintain a nice wound in the live-cell confocal imaging dishes we used for capturing cells at a high resolution. Several repeated attempts were taken to capture each single event. Another challenge was to understand whether the fact that PLP2 is located at cell–cell junctions controls the transmission of the leading-edge migration velocities or persistence towards the follower cells, using kymograph analysis. We studied several biophysical papers to understand how to correctly interpret the data from this assay.

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

For me it was really very exciting to observe the cells migrating together while forming extensions at the leading edge. During the confocal live-cell imaging session when I first observed that our candidate protein PLP2 is present at the extensions, it was really a ‘eureka’ moment for me. Indeed, discovering the loss of function in PLP2-depleted cells was another memorable moment.

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

Journal of Cell Science is a long-established journal in the field of cell biology and publishes research work related to numerous cell biology concepts. The topic of our manuscript is CCM during cancer, which is one of the novel cell biology aspects in current research. Therefore, we found JCS to be a suitable journal for the research focus of our study. Moreover, the extensive review process at JCS helps to improve the quality of a manuscript, which our lab had also experienced previously. The Open Access publication policy of the journal also helps to gain visibility of the research among our peers.

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

This project would never have been accomplished without the timely intervention of Dr Sunando Datta in the computational studies. It was during the first wave of COVID-19 in India when we just began to understand that PLP2 might play a role in CCM, and a lot of new analyses were required. He then took the initiative to learn how to implement the computational studies, particularly particle image velocimetry analysis of the collectively migrating cells. The extensive analysis and discussion carried out by us during that period will be a lifelong memory throughout my scientific career.

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?

My research career began during a master's degree course in pharmacy, where I came across the late Dr Tuhinadri Sen as my mentor, who had spent a substantial period of time in his postdoctoral work studying recombinant G-protein-coupled receptors. Indeed, working in his lab at Jadavpur University, India, motivated me to seek a career in research and apply for a research scholarship abroad. For my PhD, I joined the lab of Dr Lin Qingsong at the National University of Singapore, where I learned how to approach complex cell biology problems using high-throughput proteomics. As I dived deeper into aspects of cellular behavior and how to solve the puzzle of a mechanism adopted by the cells, I became interested in extending my career in science.

PLP2 (yellow arrowheads) localizes to the leading edge of collectively migrating cells. White arrowheads indicate the direction of migration. Scale bars: 15 μm.

PLP2 (yellow arrowheads) localizes to the leading edge of collectively migrating cells. White arrowheads indicate the direction of migration. Scale bars: 15 μm.

Who are your role models in science? Why?

My role model in science is Professor Marie Curie, who devoted her entire life to chasing after a scientific problem. I wish I could dedicate myself to scientific problems like she did and cherish the beauty of cell biology.

What's next for you?

I have already had an extended research career of around 9 years after my PhD, continuing to work at the bench. Currently, I prefer to take a break from benchwork and stay connected with research, while guiding students at master's and PhD level. Simultaneously, I am applying for independent research grants in India, as well as internationally, where there will be scope for mentoring students working on the project while I take on the role of supervisor. I would like to continue to do research in the field of cell migration and the various types of CCM exhibited by cancer cells at different stages.

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

I have always been fascinated by art, despite studying science. In time I realized that, although these are two different disciplines, a scientist probably needs to be a good artist too, or rather, the two are inseparable. Currently I am in the initial stages of launching a small start-up creating acrylic artworks that depict multiple aspects of daily life.

PLP2 drives collective cell migration via ZO-1-mediated cytoskeletal remodeling at the leading edge in human colorectal cancer cells
J. Cell Sci.