Work done in the lab of Dr. Tamal Das at Tata Institute of Fundamental Research, Hyderabad.
About author
Purnati Khuntia is a Microbiology graduate from University of Delhi (M.Sc. and B.Sc. Microbiology). She is pursuing her PhD. in Cell Biology/Mechanobiology from the Collective Cell Dynamics Lab under Dr. Tamal Das from Tata Institute of Fundamental Research, Hyderabad. She is trying to address how the Golgi polarity change occurs during collective cell migration, and its importance in wound healing. Beyond a passionate researcher in the lab, Purnati likes Cycling and Badminton, and exploring Philosophy of Absurdism.
Interview
How would you explain your research outcomes to the non-scientific community?
The human body contains millions of cells working together for the body to function properly. One subgroup of the cells, called epithelial cells, is constantly maintaining a barrier against foreign particles. Human skin is one key example of such barriers. The skin provides continuous protection against unwarranted particles trying to enter our bodies. However, because of damage to the skin in the form of wounds (scratches or a cut), it creates a gap and an opportunity for unwanted particles to enter our body.
To seal this gap, epithelial cells undertake the extraordinary task to close the wound. To close the wound, the epithelial cells move towards each other (Epithelial cell migration), from all sides of the wound. During this cell movement, the epithelial cells have to change/rearrange the intracellular content to help them move better. In an uninjured, healthy epithelial cell, the cell nucleus stays at the bottom of the cell, and organelles like the Golgi apparatus and centrosome remain on top of the cell nucleus. This specific position of Golgi with respect to the cell nucleus is fundamental to epithelial cells and defines the cell orientation, also known as cell polarity. In healthy epithelial cells, Golgi on top of the nucleus denotes the apico-basal cell polarity. Interestingly, during wound healing induced epithelial cell migration, the Golgi apparatus and centrosome shift from atop the nucleus to in front of the nucleus, known as the front-rear cell polarity. This switch in Golgi position is a very fundamental aspect of epithelial cell migration, and over the years it has become an indicator of cell migration behavior. But how the Golgi position changes its position with respect to the nucleus has remained unsolved for many decades.
To solve this puzzle, we closely looked at cells starting from apico-basal polarity to front-rear polarity, and followed Golgi position throughout the change. To our surprise, we found that Golgi undergoes a transient dispersion around the nucleus where it takes up a ring-like organization around the nuclear equator.
This discovery pushed us to ask, why Golgi dispersion into a ring-like position around the nucleus is important for epithelial cell migration? We designed a simple experiment to answer this question. Since this Golgi dispersion is induced upon epithelial cell migration, we reasoned that a comparison of cell migrations properties with or without the Golgi dispersion should demonstrate the importance of the process. We studied the cell migration behavior in two Set-ups, 1: Cells which go through the Golgi dispersion, 2: Cells which do not go through Golgi dispersion. In Set-up 1, the cell migration occurred normally. Interestingly, we found that in Set-up 2, cell migration occurred in a random direction. Instead of moving towards the wound to seal the gap, the cells moved in a random direction. Thus, possibly causing a slow wound healing. To conclude, our discovery of Golgi dispersion around the nucleus is essential for normal wound healing.
How do these findings contribute to your research area?
Our discovery brings to light one key-step which has been missed out over the last few decades in the field of epithelial cell migration during wound healing. We believe further research on epithelial cell migration in context of Golgi dispersion around the nucleus will help the field in understanding wound healing in greater detail.
“Our discovery brings to light one key-step which has been missed out over the last few decades in the field of epithelial cell migration during wound healing.”
What was the exciting moment during your research?
There were several exciting moments, but one of top ones would be the discovery of cell migration induced Golgi dispersion itself. You get goosebumps when you realize you have discovered something new that has been missing in the field.
What do you hope to do next?
In the future, I want to explore collective cell behavior in developing organs. In developing organs, along with migration, cells also undergo rearrangement in their position as well. How the organelles inside the cell behave in such an environment with multiple stimulations is definitely very interesting.
Where do you seek scientific inspiration from?
For me, getting into science was majorly driven by the curiosity to know more! Seeing something happening at a very small scale (micrometers!), and wondering how it happens.
But, doing research takes more than just wondering. And for that, asking the right question, following an intuition and executing it the right way, comes from our guide Tamal Das.
How do you intend to help Indian science improve?
I believe doing science is a collective effort of Homo sapiens to understand the Universe better. But it is definitely worth praising how the quality of Indian science is rising every day. In future, I hope to interact with students at school level and try to ignite the curiosity to know more. If I manage to establish my own lab, I would like to have regular open-days where school students can come and interact with researchers.
Reference
Khuntia P, Rawal S, Marwaha R, Das T. Actin-driven Golgi apparatus dispersal during collective migration of epithelial cells. Proc Natl Acad Sci U S A. 2022 Jun 28;119(26):e2204808119. doi: 10.1073/pnas.2204808119. Epub 2022 Jun 24. PMID: 35749357; PMCID: PMC9245705.https://www.pnas.org/doi/10.1073/pnas.2204808119