Interview with Piyush Daga

Piyush was one of the three-minute talk presenters at our recent science communication event, SciCommConnect. At the event, which we co-hosted with the Node and preLights, we were treated to fantastic talks on a range of topics. Piyush’s talk really stood out to us, not least because of the striking microscopy image on his slide. Piyush has kindly allowed us to share his presentation and we caught up with him to learn more about his research and his involvement in science communication.

How did you first became interested in science and what was your career path so far?

I really loved science classes at school. While most of my family have traditionally studied business or accounting, my parents were extremely supportive of me studying science. At school, I always liked working at the bench rather than sitting in the classroom. I pursued environmental science for my bachelor’s degree, which was a new subject in India at that time, but I also had life sciences and chemistry as a part of my curriculum. Then, I moved to Pune for my masters in biochemistry. After my masters, I joined the Collective Cellular Dynamics lab (CCD lab; nothing to do with Café Coffee Day) at Tata Institute of Fundamental Research (TIFR), Hyderabad to pursue my PhD. It was here that both mechanobiology and mitochondrial biology caught my attention. Both these topics were new to me then and thanks to my advisor Dr Tamal Das, I had the opportunity to explore many things independently. So far, it has been an exciting journey to pursue mitochondrial research from a mechanobiology perspective!

We heard an overview of your research in your three-minute talk, but can you tell a bit more about your work?

In biological tissues, a delicate synergy exists between the extracellular matrix (ECM) and the cells embedded in it, so much as that the state of a cell can only be defined if the mechanical microenvironment is also known. In fact, the ECM exhibits a remarkable diversity in its biochemical, biomechanical and organizational properties across different tissues, regions within a tissue and various physiological states. Mechanical cues arising from the stiffness of the ECM elicit an intracellular tensional response that modulates cellular forms and functions, ensuring tissue homeostasis. As numerous studies have shown, this modulation depends on the stiffness-dependent remodelling of cytoskeletal elements and cell-matrix adhesions which further drives changes in nuclear activities. In contrast, very little is known about how other intracellular organelles respond or adapt to mechanical forces. I was particularly interested in mitochondria because, being the central players in metabolism, they have the potential to drive the different layers of mechanotransduction. Being tethered to the cytoskeleton, mitochondria also experience constant tension. Hence, my quest to understand how mitochondria adapt and respond to mechanical cues began.

To sum up my PhD work, mitochondria adapt to differences in ECM stiffness, both in terms of how they appear (morphology) and how they are distributed (localization) within the cell. We mimicked different tissue stiffness conditions using hydrogels and found that the mitochondria of cells within a soft ECM were filamentous and elongated, and were uniformly distributed through the cytoplasm. However, on a stiff ECM, mitochondria were fragmented and clustered near the nucleus (perinuclear clustering). My next goal was to understand the process molecularly and to decipher the physiological relevance of this unique perinuclear clustering of mitochondria.  We found that filamin, which is an actin binding protein, showed different localization patterns under soft and stiff ECM conditions. Filamin proteins were highly enriched near the nucleus on stiff ECM and this perinuclear enrichment was the key factor driving the perinuclear clustering of mitochondria. For the functional relevance part, we turned to a different setup, namely, mesenchymal stem cells (MSCs). Firstly, we confirmed that the stiffness sensitive changes in mitochondrial morphology and localization occurred in MSCs. The localization changes were also driven by filamin. Finally, from a stem cell differentiation point of view, we wanted to check if organelle positioning, particularly mitochondrial positioning, had any role in priming these stem cells towards an osteogenic or a bone cell fate on stiff ECM. We found that when the mitochondria were clustered around the nucleus, the osteogenic marker RUNX2 was expressed inside the nucleus. We tried different ways of perturbing this mitochondrial clustering and found that in each case, the nuclear signal of RUNX2 was reduced. This led us to conclude that the perinuclear clustering of mitochondria played a crucial role in osteogenic differentiation. Overall, our work showed that not only do mitochondria respond to mechanical forces but also their specific positional arrangement within cells can influence cellular identities.

Are you now coming towards the end of your PhD?

Yes, I had my PhD defense a couple of months ago, so I’ve finished.

Congratulations! So, what’s next for you?

I am still thinking about what I want to do next. I know that eventually I want to move to research that is of clinical relevance. I have an interest in the heart because both ECM stiffness and mitochondrial dynamics are very relevant to cardiac development. The liver is another exciting model to work on as liver fibrosis is marked by increased ECM stiffness. The liver is quite intriguing because it has high metabolic sensitivity, and the mitochondria behave very differently in different parts of the liver. I’m in the process of applying for postdoctoral positions to continue researching mechanobiology of organelles and organelle contact sites.

Why do you think science communication is important, and can you tell us about any other science communication projects you’ve been involved in?

During my PhD, I volunteered for almost all the science communication or science outreach events that happened at our institute. Interestingly, I’ve noticed the number of such events increasing over this period. In the last 6-7 years, I have been actively involved in organizing science fairs, SciArt exhibitions, science open days for schools and colleges, as well as visiting schools and talking to students about science and research. But one thing that I’ve really wanted to do was to create a science drama. Soon after the COVID pandemic, I had the opportunity to do this along with three of my colleagues Aravind, Sinjini and Aaheli at TIFR Hyderabad. We wrote a science play about COVID19 called “Spikes Up” where we demonstrated how the disease affects the human body. It was extremely dramatized, over the top, full-blown entertainment. We personified the major body parts and organs that COVID19 affects and showed how the disease symptoms and organ functioning vary between vaccinated and unvaccinated people. We even had a fight scene where the vaccine army (the immune cells) defeats the COVID army! Almost 200 students watched this play which we performed a couple of years ago and the school kids really loved it. This was a major item ticked off my bucket list!

Currently, I’m involved in science theatre through the Science Media Center at TIFR, Hyderabad. We acquired the rights to perform the play “The Square Root of a Sonnet” written by Nilanjan P. Choudhury. This play explores the intriguing and complex relationship between two astrophysics giants – the Nobel Laureate Subrahmanyan Chandrasekhar and his mentor Sir Arthur Eddington. It is a story of ambition, friendship and betrayal set against the backdrop of the two world wars, the Indian freedom struggle and the birth of the strange new sciences of relativity and quantum mechanics. We are gearing up for public shows of this play very soon. It has been a great opportunity to be a part of this endeavour.

In the future, I would love to make scientific concepts accessible in the form of science theatre, or science educational theatre. I think taking such plays to schools, colleges and public spaces could help popularize science as well as create scientific temper and curiosity.

What role do you think microscope images should play in science communication?

Whenever we have school or college students visiting our institute, we always show them the microscope, and they are fascinated by the images. It can be something as simple as the nucleus and actin. So, I think microscope images play an extremely important part in science communication. In addition, visuals are the best way of communicating science! And cells and tissues are extremely pretty to look at and provoke curiosity in people of all ages. One interesting question that I always encounter is, ‘why is the nucleus blue; do you put blue color into it?’ As an answer to this query, I share the concept of fluorescence and how visualizing anything within the cell works. If you give people examples of medical testing where you have an x ray or an MRI, they are able to connect the science very well with their personal experiences. I believe microscopic images will always be at the top of science communication projects.

Speaking of linking the science to people’s experiences, in your talk, you had to pick out some key points, but you also included some popular culture references. How did you go about choosing what you were going to include in your three-minute presentation?

When I was preparing for my presentation, a key goal was that I should not get bored of what I’m going to talk about. And to keep things relatable, my reference point was my parents and grandparents. Even, if they could not understand the whole talk, they should be able to understand at least 30-40% of what I do. Interestingly, I’ve just been back home, and there was a big celebration in my society. Someone asked me to explain my research in a minute. I could not do this in English, because most of the people there could not understand, so I fumbled for a bit. I somehow managed to explain my research using simple terms and analogies in Hindi, my mother tongue. I hope they took home the main message. I think my training in teaching younger students and in science outreach helped me. I watch a lot of movies, and I have a theatrical side to me! I am aware that too much of jargon won’t work, and hence it’s important to draw on to analogies from popular culture to drive home the point. Less jargon, simple language and a dash of humour: these were the key things I kept in mind before preparing for my talk.

You also caused a slightly controversial moment by saying the mitochondria is formerly known as the powerhouse of the cell. So, what should the mitochondria be known as now?

Well, I did not intend to create that controversy. Actually, when my manuscript was under review, a couple of reviewers mentioned that using the word ‘powerhouse’ was redundant. I completely agree, but because it has been used so frequently, people remember it even if they’ve not pursued science at a higher level. I always tell my friends that it’s much more than just the powerhouse of the cell! A review paper suggested that mitochondria should be called the motherboards because of their critical role in cellular operations. If the nucleus is the brain of the cell, then mitochondria should be the motherboards and not just the power cords.

Finally, what were your main takeaways from the SciCommConnect workshop?

Everyone did a fantastic job presenting their research within 180 seconds. Although there were diverse research topics, I was happy to see a lot of mechanobiology being done all around the world. I enjoyed listening to every talk. It also made me realize how difficult it is to condense years of research into three minutes. Personally, it was a great opportunity to reflect back on those many years of research and try to pick out the major highlights. I also enjoyed Jamie’s talk and the networking session. Overall, the exposure to such a format was extremely enriching and I’ve already pitched the idea of a three-minute research talk to the Science Media Center at my institute.

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