First person – Arindam Ray and Yashashwinee Rai

Arindam Ray

Describe your scientific journey and your current research focus

A.R.: I joined PhD program at JNCASR, Bangalore, India with an interest in stem cell and cancer biology. I was intrigued by the robust genetic tools in the Drosophila model that one can harness to address outstanding questions of tissue development. During my PhD, I investigated the role of conserved ESCRT machinery in blood progenitor differentiation and their lineage choice decisions, and how their misexpression may lead to hematologic malignancies. It was quite a laborious job to thoroughly characterize the role of each ESCRT core component in hematopoiesis. The rigorous analysis generated a comprehensive functional map of ESCRT in distinct progenitor subsets with many interesting observations that remain unexplored so far. Additionally, I have explored the role of organelles such as endosomes and mitochondria in blood cell homeostasis and Drosophila immunity. All these new discoveries brought me the sense of joy, happiness and satisfaction that a scientist always looks for. I love working in a collaborative environment that encourages novel ideas. Currently, I am pursuing my interest in cancer immunology and trying to understand immune cell development and function in the context of diseases such as cancer.

Y.R.: My undergraduate school played a pivotal role in tuning my interest towards research. My first research experience was at a 3-year undergraduate internship, working with Drosophila to understand neural plasticity and memory retention during metamorphosis. This gave me a taste of how exciting science can be! I'm currently a graduate student and working on this project along with Arindam has helped me find novel questions regarding progenitor heterogeneity and the role that organellar dynamics play in the process, which is now the focus of my graduate project.

Who or what inspired you to become a scientist?

A.R.: I have been drawing inspiration at various levels starting from my biology teachers at undergraduate school to my mentors and eminent scientists. However, more than any person, it was my spontaneous and innate inquisitiveness towards fundamental questions of cell biology and microbiology since my school days that pushed me to choose a career in research. So, I made the decision quite early on to become a scientist. Additionally, during my journey as a scientist, I have always looked up to the fighting spirit and never-give-up attitude of sports personalities like Sachin Tendulkar and Lionel Messi who set the definition of hard work, grit and persistence.

Y.R.: For me, becoming a scientist was never really the plan. But preparing for medical school made me aware of the shortcomings in our understanding of biology. My late uncle, to whom I was rather close, was a bioinformatician. He nurtured my curiosity in congenital and genetic defects and encouraged me to pursue research. Through him, I was able to secure a chance to explore this exciting field and make it my career. Whenever I feel disappointed, I try to remember the joy I experienced discussing science with him and channel that same exuberance into my work.

How would you explain the main finding of your paper?

A.R.: We discovered that the evolutionarily conserved ESCRT machinery that regulates endosomal protein sorting in a ubiquitous manner has diverse roles in blood progenitor maintenance and their differentiation to different lineages. This is achieved by the differential role of individual components of ESCRT towards blood cell lineage specification. We find that ESCRT components contribute to the heterogeneity of blood progenitor subsets that are developmentally distinct. Also, a few ESCRT components are essential to maintain the reserve, refractile pool of blood progenitors under steady state or upon immune challenge. We provide a functional chart of ESCRT in the Drosophila hematopoietic system that underscores the complexity of endosomal regulation during stem cell fate choice.

What are the potential implications of this finding for your field of research?

A.R.: Our finding highlights ESCRT as potential target to control hematologic anomalies. This study provides substantial rationale to test whether targeting a specific ESCRT component can improve the differentiation potential of hematopoietic stem cells, both in vitro and in vivo, for regenerative therapies.

Yashashwinee Rai

Which part of this research project was the most rewarding?

A.R.: The findings are the most rewarding aspects of this project. We have remained interested in unravelling mechanisms that control progenitor fate choice and functional heterogeneity. We found out that ESCRT is a critical molecular complex that suppresses the differentiation of refractory progenitors. We presented this work at several international conferences including the Genetics Society of America and the European Drosophila Research Conference. I won the best talk award at the in-house symposium of JNCASR for presenting this work, and won the best thesis award too in biological sciences at JNCASR. That was exciting! Both Yashashwinee and I worked very hard on this project and our mentor Dr Inamdar guided us through to bring this work to its final shape, which is amazing!

Y.R.: This project was my first as a graduate student and it proved to be an excellent opportunity to grow as a researcher. Apart from all the fun and excitement of the study, it helped me gain a deeper understanding of how research must be designed and conducted and the checks and balances to keep in mind. While being an enriching and exciting journey, it was also the avenue that led me to my current research interest.

What do you enjoy most about being an early-career researcher?

A.R.: What's most enjoyable as an early-career researcher is the learning process. While the degree of struggle at each step may range from a little to a lot, with each new milestone comes a new experience that builds the skill for higher excellence and success.

What piece of advice would you give to the next generation of researchers?

A.R.: First, it's important to identify the most important and understudied questions in the field. You must be persistent towards your goal and work hard till you get an answer to your hypothesis or questions. Enjoy the work you are doing and give your best shot.

Y.R.: Apart from what Arindam said, I would like to emphasize the need for exploration and to not lose heart. It is a good idea to accrue a wide range of experiences through internships or projects in different labs to find what truly excites you. It makes the journey more enriching.

What's next for you?

A.R.: I am currently pursuing my postdoctoral research on tumor immunity and hopefully can make significant contribution to the development of new anti-cancer immunotherapies.

Y.R.: I am currently working on my graduate project regarding progenitor heterogeneity in Drosophila blood progenitors. After this, I would love to explore new systems and study the organellar fine-tuning of biological processes and diseases.