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A story of Fatty Phagosomes

Work done in the lab of Dr. Siddhesh S. Kamat, Department of Biology, Indian Institute of Science Education and Research Pune

About author

Neelay Mehendale
Neelay Mehendale

Dr. Neelay Mehendale earned his PhD from Dr. Siddhesh Kamat’s Lab at the Indian Institute of Science Education and Research (IISER), Pune, India. Subsequently, he moved to Germany and currently he is a postdoctoral fellow at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie in Berlin. He specialises in mass spectrometry-based lipidomics and metabolomics. At present, his research work focuses on the biochemical implications of Inositol phosphates. Apart from his scientific pursuits, he is a well-accomplished Hindustani classical vocalist, and artist who performs on a regular basis. Here, Dr. Mehendale talks about his article “Mapping sphingolipid metabolism pathways during phagosomal maturation” published in ACS Publications (2021).

Interview

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

Lipids are essential for our well-being, just like proteins and carbohydrates. Lipids include different kinds of fats, oils, waxes and other complex organic (biological) substances that help us maintain our physical and metabolic health. My research involves studying the role of a kind of lipid in a specific aspect of immunity. The cells of the immune system destroy invading pathogens by a process called ‘phagocytosis’ –cell-eating. During phagocytosis, the pathogens are engulfed by the cells into vesicles called the phagosomes and get subsequently destroyed. Lipids like cholesterol, ceramides and glucosylceramides enable these phagosomes to be processed properly. Some people refer to this fat as a flavor, and these fats (or lipids) make the phagosomes healthy in terms of their cellular metabolism.

Phagosome maturation: As a phagosome matures from a nascent to a matured state, it gathers cholesterol, ceramides and glucosylceramides, resulting in the formation of a raft-life structure (seen here as blobs). These rafts subsequently serve as anchoring points for a protein called dynein, which then transports the phagosome for completion of the process of phagocytosis.
Phagosome maturation: As a phagosome matures from a nascent to a matured state, it gathers cholesterol, ceramides and glucosylceramides, resulting in the formation of a raft-life structure (seen here as blobs). These rafts subsequently serve as anchoring points for a protein called dynein, which then transports the phagosome for completion of the process of phagocytosis.

How do these findings contribute to your research area?

This study suggests a novel role of lipids such as ceramides and glucosylceramides in the process of phagocytosis. These findings have strengthened our understanding of the biochemistry underlying the process of phagocytosis. This knowledge would be useful in understanding the complexity of several diseases that arise from impaired phagocytosis like Gaucher’s disease, Fabry’s disease etc.

“Study suggests a novel role of lipids such as ceramides and glucosylceramides in the process of phagocytosis.”

What was the exciting moment during your research?

I think in the busy research life, one should stop at times to smell the roses. I find excitement in small things like observing cells happily growing in their dishes, the bubbling of liquid nitrogen etc, but there were a series of exciting moments in this study that I remember vividly. I found that the ceramides were an important component of phagocytosis, however, there were a few pieces of the puzzle that were still missing. Reading more about the glucosylceramides sparked an idea on the possibility of ceramides getting converted into glucosylceramides through an enzyme, an activity hitherto not associated with phagosomes. When I probed deeper into it, I saw that this was indeed the case! This was probably the most exciting part of the research.

What do you hope to do next?

I intend to gain further expertise on mass spectrometry in the near future. However, bringing Indian traditional knowledge back to the centre table through modern scientific research has been my long-standing goal. This was inspired by the research I performed on certain aspects of Ayurveda with Prof. Bhushan Patwardhan at the Interdisciplinary School of Health Sciences, Savitribai Phule Pune University.

Where do you seek scientific inspiration from?

Scientific inspiration is very abstract and can be driven by an urge to ‘understand’, regardless of the subject. I keep my eyes wide open because I feel that one can find inspiration in countless manners and in the most unexpected places.

How do you intend to help Indian science improve?

While contemporary research in India has advanced significantly, I believe that a multidisciplinary lens in the research process is still the need of the hour. I intend to promote awareness of our traditional systems of medicine in the scientific community by employing an interdisciplinary approach. We need to focus on these unique intersections. I also want to inspire young minds who are embarking on their research-journey to diversify their research interests and incorporate traditional knowledge in their multi-faceted research.

Reference

Neelay Mehendale, Roop Mallik, and Siddhesh S. Kamat. Mapping Sphingolipid Metabolism Pathways during Phagosomal Maturation. ACS Chem. Biol. 2021, 16, 12, 2757–2765. https://pubs.acs.org/doi/10.1021/acschembio.1c00393

Edited by: Neha Varshney

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