Beyond oxygen transport: Exploring red blood cells with a new lens

Work done in the lab of Prof Sandeep M Eswarappa at Dept. of Biochemistry, IISc Bangalore.

About author

Sangeetha obtained her Bachelor’s of Science degree in life sciences from Bhavan’s Vivekananda College, Hyderabad. She then joined the Indian Institute of Science, Bangalore in 2015 as an integrated PhD student. She is currently pursuing her PhD under the mentorship of Prof. Sandeep M Eswarappa at the Department of Biochemistry.

Her research interests include cell biology and translational research. These were curiosities that were kindled by her fascination to understand what happens inside a microscopic cell. Answering the unanswered questions in these fields continues to be an exciting proposition to her. When not in the lab, she likes to read books, sketch, and watch movies.

Interview

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

Proteins are known as “building blocks” of the human body and it is believed that proteins are synthesised by every live cell except the red blood cells (RBCs). RBCs are cells that contain hemoglobin and carry oxygen to the body and take away carbon dioxide. These cells also have a long life span of 120 days, which is a long time for a cell to survive without making new proteins.

Our study addressed this fundamental question: Can RBCs aka erythrocytes make their own proteins? Using different techniques to study protein synthesis, we discovered that indeed these cells can make their own proteins. We were also able to visualise the translation machinery, called ribosomes, for the first time in these cells. We also identified that the proteins that make up hemoglobin; alpha globin and beta globin, were the proteins that were made in these cells. When translation was inhibited, the levels of these proteins reduced, reaffirming our observations. Overall, our study has answered a very fundamental question in RBC biology.

Schematic showing the different methods to visualise proteins being synthesised in red blood cells. In the first panel, ribosomes can be seen as pearls on a string under an electron microscope, forming long chains, which is indicative of protein synthesis. In the second panel, a radioactive signal in the [35]S-methionine lane indicates that the radioactive amino acid is being taken up, suggesting active protein synthesis. In the third panel, fluorescence signal is observed in a red blood cell which is a measure for new proteins being made.

How do these findings contribute to your research area?

Hemoglobinopathies are disorders in the protein hemoglobin, which forms the bulk of the red blood cells. Current therapy for such disorders focuses on manipulating this protein within the precursor cells of RBCs, which is very challenging. Discovery of the process of translation in these cells opens up new avenues to treat such disorders by targeting the red blood cells, which are more easily accessible.

“Our study has answered a very fundamental question in red blood cells biology.”

What was the exciting moment during your research?

One of the earliest experiments we had done to study protein synthesis is called S35 methionine labelling, wherein the amino acid methionine is radioactive and if protein synthesis is active, it gets incorporated into the newly synthesized proteins. When I developed the radioactive gel and observed a black blotch in the experimental sample at the expected size, I was elated beyond words. It was and will remain the most beautiful blotch I have ever seen.

What do you hope to do next?

Translational research has always been my passion. I believe in the phrase “Bench to Bedside”. I hope to develop new ways to treat RBC-related disorders with the knowledge that I have gained from my research work.

Where do you seek scientific inspiration from?

The endless unanswered questions about how our human body works inspire me to ask the most difficult questions in biology. Nature and life in itself is where I draw my inspiration from.

Having a mentor with a vision has also helped me look at scientific problems with varied perspectives. My PhD mentor, Prof Sandeep M Eswarappa has been my greatest inspiration. He has taught me that asking the right questions is work half done. I hope to carry this attitude throughout my life.

How do you intend to help Indian science improve?

Besides doing science, I believe communicating science is also a crucial part in kindling the passion for science in the younger generation. I have been interested in science writing from when I started my research work. I have written a few articles for our institute’s magazine (IISc Connect) and newsletter (IISc Kernel). I wish to continue doing my part to write about exciting science that’s happening around the country and over the globe and hope to inspire more students to venture into the endless ocean that is science.

Reference

Sangeetha Devi Kumar, Debaleena Kar, Md Noor Akhtar, Belinda Willard, Debadrita Roy, Tanweer Hussain, Purusharth I Rajyaguru, and Sandeep M Eswarappa; Evidence for low-level translation in human erythrocytes, Molecular Biology of the Cell, 22 September 2022; Vol. 33, No. 12. Doi: https://doi.org/10.1091/mbc.E21-09-0437

Copy Editor

Pragya Gupta

PhD Scholar, University of Melbourne, Australia

Beside being a passionate stem cell researcher, Pragya Gupta is trained in Indian classical music, enjoys baking, inventive craftwork and learning about different cultures. She is currently doing her PhD at the University of Melbourne in Australia, where she is researching new ways to treat brain cancers.

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