Maintaining skin barrier – our first line of defense

Work done in the lab of Prof. Mahendra Sonawane at Tata Institute of Fundamental Research

About author

Kirti Gupta conducted her PhD work under the guidance of Prof. Mahendra Sonawane at Tata Institute of Fundamental Research, Mumbai. She completed her BSc. In Biomedical Sciences from ANDC, Delhi University and MSc. from School of Life Sciences, JNU, New Delhi. She is a cell and developmental biologist, interested in understanding the process of morphogenesis. She also served as a visiting faculty at Centre of excellence in Basic Sciences, University of Mumbai.

She has now moved to The Francis Crick Institute, London as a research scientist to study organ morphogenesis by looking at heart development.

Interview

How would you explain your research outcomes to the non-scientific community?

Our skin functions as the first barrier to protect us from physical and chemical assaults as well as any harmful pathogens and hence, it is of utmost importance that it maintains its integrity to prevent any breach into our bodies. Skin is made up of layers of skin cells scientifically called keratinocytes, which are of a characteristic size and shape and stick to each other and the tissues underneath to form a strong well defined wall. Interestingly when the body changes size, i.e., during growth or injury, skin also must expand or contract. In my Ph.D. work, I studied the mechanisms which allow skin cells to change their size and shape, and hence maintain the intact cover over the body under stress conditions. I found that two consecutive steps – lipid synthesis and its directed trafficking to the cell membrane- coordinate with each other to allow cells to grow and maintain the tissue homeostasis.

A schematic of Myosin Vb isoforms showing different outcomes depending upon their interaction with either Rab11 or Rab10. Although Myosin Vb-Rab11 interaction is essential to maintain the cell size during development, presumably by regulating recycling of the apical endosomes, MyosinVb-Rab 10 interaction regulates the apically directed transport from TGN downstream of the mTOR-FASN axis, during compensatory cell growth.

How do these findings contribute to your research area?

I studied the phenomena of compensatory cell growth during development to show that cell morphometry plays an essential role in allowing the cell to increase their size under stress conditions and offered the role of an isoform of a motor protein called Myosin Vb in guiding the directional trafficking is essential to allow apical expansion of cells to maintain tissue homeostasis. Furthermore, this study showed a putative mechanism of crosstalk between cellular metabolism and trafficking to allow synchronous growth of the skin cells, which has so far remained unraveled. We also found a unique role of Golgi morphological adaptations in mediating this process. Hence, this study helps us to understand the process of cell growth in a holistic manner.

“This study helps us to understand the process of cell growth in a holistic manner”

What was the exciting moment during your research?

It gives me immense pleasure to look inside the cells with the help of powerful microscopes and observe the behavior of various subcellular components performing their functions faithfully in the middle of chaos. I was super excited to look inside the skin cells of a living embryo to see the tiny vesicles -packets of lipids and proteins- moving from Golgi to the membrane. These observations stunned me and helped me ask the right questions for my research.

What do you hope to do next?

I currently work as a research scientist at The Francis Crick Institute in London. I am pursuing my interest in studying cell behavior in building organs by studying heart development. My love for science has reached from skin to heart, as I jokingly like to say.

Where do you seek scientific inspiration from?

I was very fortunate to have studied with exceptional scientists during my Ph.D., master’s, and bachelor’s. I find it inspirational how scientists centuries ago derived logical conclusions from simple yet clever experiments, and scientists now continue to accomplish so with the help of increasing knowledge and technology. Reading their work- related or unrelated to my research interest keeps me motivated.

How do you intend to help Indian science improve?

I feel Indian science can gain hugely from exposure to world-class research in early career/school days. I was fortunate to get exposure to research during my undergraduate studies, which sowed the seeds of scientific curiosity and familiarized me with how research works and helps society. Bridging the link between scientific institutes and schools/undergraduate colleges, which is limited to very few elite institutes in India so far, will allow more and more people to feel optimistic about taking up research as a profession.

Also, I think Indian graduate students are relatively unaware of the prospects other than academia, which can be overcome by exposure to para-academic/industrial research during Ph.D. and should be supported by graduate schools. It will allow students to be more exploratory in their career and reduce job insecurity and confusion post Ph.D.

Reference

Kirti Gupta, Sudipta Mukherjee, Sumit Sen, Mahendra Sonawane; Coordinated activities of Myosin Vb isoforms and mTOR signaling regulate epithelial cell morphology during development. Development 15 March 2022; 149 (6): dev199363. doi: https://doi.org/10.1242/dev.199363

Copy Editor

Kshipra S. Kapoor

Ph.D. candidate at Rice University

Kshipra has completed Bachelor’s in Biomedical engineering from University of Mumbai where she was the recipient of institute gold medal and university bronze medal for obtaining the highest GPA in her cohort. She received her master’s degree in Electrical and Computer Engineering at Rice University. She is currently a Ph.D. candidate at Rice University, where she is working with Prof. Raghu Kalluri in the field of exosomes. Specifically she is interested in dissecting the exosome heterogeneity between healthy and cancer cells-derived nanovesicles and advancing the understanding of exosomes classes in cancer. In her spare time, Kshipra enjoys keeping fit, cooking, calligraphy and family & friends.

Kshipra is also involved in various professional development programs and as a first generation-PhD student is helping amplify the voices and stories of minorities in her field via the global organization she is part of snevresearch where she manages the events.

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