Mitochondrial Topoisomerases of the human malaria parasite Plasmodium falciparum

Work done in the lab of Dr. Sunanda Bhattacharyya, Department of Biotechnology and Bioinformatics, at the School of Life Sciences, University of Hyderabad, India

About author

Priyanka Singh is a CSIR-Senior Research fellow in a malaria research laboratory at the University of Hyderabad, Telangana, India. She undertook her Masters in Biochemistry from the same university. Priyanka specializes in the field of molecular parasitology and finds herself inclined to delve deep into malarial research. Currently her research attempts to unravel a unique type II topoisomerase as a future drug target to cure malaria. Besides being a research scientist peering into microscopes, she indulges her artistic side through her talent and passion in singing.

Interview

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

Research in malaria is crucial to better understand the illness, create efficient preventative and treatment plans, and ultimately fight towards its eradication. During my research I investigated the function of a novel Type IIB topoisomerase i.e., Topoisomerase VIB and Spo11 in malaria parasite Plasmodium falciparum. Earlier, it was shown that these two proteins form a functional Type IIB topoisomerase enzyme in plants and algae and they are required to untangle the DNA during endoreduplication which is essential for the plant growth and development. This endoreduplication also occurs in the malaria parasite and is essential for its survival and re-infection.

Within the malaria parasite, we found that Topoisomerase VIB and Spo11 physically associate with each other to form a functional holoenzyme. Since TopoVI has previously been linked to the segregation of interlinked DNA, this discovery is significant.

Mitochondria is the structure inside cells that produce energy and have its own DNA. Proper segregation of mitochondrial DNA is important for maintaining the integrity and function of mitochondria. However, the mechanisms involved in this process, particularly in the malaria parasite, have not been well understood. Our study suggests that the Type IIB topoisomerase in Plasmodium i.e., Topoisomerase VIB and Spo11 may have a role in ensuring the proper distribution/segregation of mitochondrial genome during segregation. Understanding this mechanism, could lead to development of new strategies to target the malaria parasite and disrupt its survival and reproduction.

How do these findings contribute to your research area?

Malaria is a life-threatening disease transmitted by mosquitoes, and it affects millions of people around the world, particularly in tropical regions. My research outcomes contribute to the development of better strategies for preventing and treating malaria. Our investigation into the function of the topoisomerases in the mitochondrial biology of the malaria parasite, and identification of a unique Topoisomerase VIB, which is crucial for maintenance of the mitochondrial genome, open new doors to potential therapeutic interventions. Our study holds promise that this topoisomerase can be used as an effective anti-malarial target. In future, our study aims at identifying a specific inhibitor of this topoisomerase and investigating its effect in parasite growth.

“Our investigation into the function of the topoisomerases in the mitochondrial biology of the malaria parasite, and identification of a unique Topoisomerase VIB, which is crucial for maintenance of the mitochondrial genome, open new doors to potential therapeutic interventions.”

What was the exciting moment during your research?

Research is a complex and demanding process, often involving moments of epiphany and excitement. There were many such moments during this research. The most exciting moment was when we successfully validated the unique expression of the both the subunits of the Topoisomerase VI i.e., PfTopoVIB and PfSpo11 inside the malaria parasite Plasmodium falciparum at the late-schizont stage of the parasite, by using multiple approaches. Further, utilizing various molecular and cell biology approaches, we could establish their likely role in the segregation of mitochondrial genome of the parasite that occurs during endoreduplication.

What do you hope to do next?

My primary goal as a researcher is to pursue the development of knowledge and have a positive impact on scientific advances in the field of molecular parasitology. I am interested in learning more about the complex molecular connections that occur between parasites and their hosts. Finding novel targets that parasites use to enter and infect host cells can lead to creation of novel medicines and interventions of the age-old disease like malaria.

Where do you seek scientific inspiration from?

During my scientific journey, I was inspired by several individuals at different stages of life. Starting from my brother who showed all kinds of curiosity since childhood towards learning the wonders and complexity of the natural world. During my Masters, sharing scientific knowledge with a wider group of people through conferences, writing, or engaging in science outreach activities were a major source of inspiration. My mentor, Dr. Sunanda Bhattacharyya, strongly motivated and inspired me throughout my journey to think critically and do quality research.

How do you intend to help Indian science improve?

As a molecular parasitologist my goal is to actively take part in collaborative research, building capacity, disseminating knowledge, and advocate policies, to help understand and manage parasitic diseases in India. We can collaboratively advance science and make great progress against deadly diseases in the nation.

Reference

Priyanka Singh, Wahida Tabassum, Nupur Fangaria, Sandeep Dey, Siladitya Padhi, Mrinal K. Bhattacharyya, Kota Arun Kumar, Arijit Roy, Sunanda Bhattacharyya. Plasmodium Topoisomerase VIB and Spo11 Constitute Functional Type IIB Topoisomerase in Malaria Parasite: Its Possible Role in Mitochondrial DNA Segregation. Parasitology 2023. DOI: https://doi.org/10.1128/spectrum.04980-22

https://doi.org/10.1128/spectrum.04980-22

Copy Editor

Nivedita Kamath

Postgraduate in Biotechnology

Nivedita is a Postgraduate in Biotechnology, with one year Project Assistantship experience at inStem, DBT. She is currently a UPSC aspirant planning to appear for 2021 CSE. Although switching from science career to focus on governance policy and administration, her love for science remains ever-etched in all that she does. On her journey from a researcher toward public administrator, she believes in the critical role of science communication and journalism in bridging the gap between lab benches and public fields. Being part of BioPatrika is her being one stone laid for that very bridge.

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