Work done in the lab of Prof. Richa Rikhy at Biology Department, IISER, Pune, India
About author
Dr. Dnyanesh Dubal is a postdoctoral research associate at the Department of Clinical Neurosciences and MRC-Mitochondrial Biology Unit (MBU), University of Cambridge, United Kingdom. He completed his Ph.D from reputed Indian Institute of Science Education and Research (IISER), Pune, India under the supervision of Prof. Richa Rikhy. During Ph.D, he studied the role of mitochondria in neural stem cell development using the Drosophila brain as a model system. At IISER, he also worked as a program coordinator in Disha organization which works for science education for underprivileged students in Pune. His research interests are mitochondrial disease biology, nuclear metabolism and stem cell biology. Apart from research, he is also interested in pedagogy and origami.
Interview
How would you explain your research outcomes to the non-scientific community?
All biological systems ranging from unicellular to multicellular organisms require energy to perform different activities such as cell division, movement, reproduction etc. In eukaryotic cells, this biochemical energy is in the form of adenosine triphosphate (ATP) which is produced by small organelles called mitochondria. Hence mitochondria are considered as a powerhouse or cellular batteries of the cell. In the past few years, mitochondria received considerable attention due to its involvement in other important cellular processes and various diseases. These are highly dynamic, double membranous organelles and continuously undergo cycles of fusion and division depending on cell type, cell cycle stage and demand of the cell. Cells are high on ATP when fused mitochondria happens and low when fragmented. There is dedicated protein machinery involved in the regulation of mitochondrial shape transition and mutation in these causes several diseases like optic atrophy, Parkinson’s disease etc. During Ph.D., I decided to decode the function of mitochondrial dynamics proteins in neural stem cell development using the developing brain of Drosophila melanogaster a.k.a. fruit fly as a model system. A brain is particularly heavily dependent on mitochondria for energy requirement and particularly susceptible to mitochondrial dysfunction. Defects in the mitochondrial function cause several neurodegenerative disorders. Neural stem cells (NSCs) are specialized cells with high proliferative capacity present in the brain. They are responsible for the production of functional cells of the brain such as neurons and glia. Since there is less information available on such an important aspect of brain function, we decided to take up the work and it became the main focus of my Ph.D program: working on Drosophila NSCs to decode the importance of mitochondrial role in stem cell maintenance.
About 70% of human disease related genes are similar (homologs) to Drosophila and hence many researchers and scientists use this fruit fly for their experimental work. Initial plan of our study was to manipulate the process of fusion (synthesis) and fission (fragmentation) proteins and then examine their effect on NSCs proliferation and differentiation. In cells, genetic information flows from DNA → RNA → Protein. After the protein is synthesized, it carries out different functions in the cell. In our study, these Proteins of interest were proteins involved in mitochondrial dynamics regulation. We downregulated mitochondrial dynamics proteins in NSCs of the Drosophila larval brain. Next, we assessed the effect of these manipulations on NSC growth, differentiation, cell death and energy status of NSCs. We found that inhibition of mitochondrial fusion in NSCs caused production of fewer neurons compared to control NSCs. When fusion was restored, neuronal populations were rescued which confirmed that mitochondrial fusion is essential for the NSC development. This study has shown that unlike many other stem cell types, NSC development is dependent on the fused state of mitochondria. For more details, please go through my research article published in the PLoS Genetics.
How do these findings contribute to your research area?
How mitochondria communicate with signaling pathways to determine cell fate is a fundamental question in mitochondrial biology. In this study, we have uncovered a critical mitochondrial function in regulation of NSC development in the developing brain. This study will help to improve understanding of mitochondrial role in stem cell development. Despite the fundamental nature of the research, it has opened several interesting avenues of studying mitochondria in the context of stem cell development which has potential to develop therapeutic techniques to treat neurological and mitochondrial disorders.
“This study will help to improve understanding of mitochondrial role in stem cell development.”
What was the exciting moment during your research?
Research is full of exciting moments. It always gives me an adrenaline rush when I get something novel and exciting. However, my first exciting moment in research was when I was looking at the green fluorescent protein (GFP) expressing Drosophila flies under the fluorescence microscope. It is when I realized how this small and simple molecule has revolutionized biology and deserved the Nobel prize for its discovery. Later during Ph.D., there were several exciting moments like traveling abroad for conferences, discussions with Nobel laureates, receiving best poster award, getting free merchandise from roadshows are few of many.
What do you hope to do next?
Mitochondria are really fascinating organelles. I would like to further continue my research on understanding how mitochondria contribute to the decision-making process of cell development. This includes studying the effect of mitochondria on nuclear gene expression and epigenetic regulation. Apart from my research, I am also interested in teaching biology to college students. To pursue this, I am hoping to get affiliated with colleges in Cambridge.
Where do you seek scientific inspiration from?
There is no one particular inspiration source. Research papers with innovative experiments, conferences and workshops in which giants in the field present their simple ideas but greater impact research work, discussions with scientists are my key inspirational sources.
How do you intend to help Indian science improve?
During my Ph.D, I worked with multiple NGOs in science education. I got the opportunity to interact with students from different socio-economic backgrounds. I found tremendous potential in those young minds. If they get an opportunity to learn in reputed Indian institutes with international recognition that would definitely give them greater opportunities to pursue their dreams. By keeping this in mind, I, with my other friends at IISER-P, started a program for class 11th and 12th students on an experimental basis with a vision to get these students admitted to prestigious Indian institutes like IISER, IIT. To our surprise, two out of three students of the first batch could get admission in IISER and IIT. This gave us confidence and motivation to further continue this program. I intend to continue this after going back to India.