Hello, Vinay! Why don’t you start at the beginning? What has been your journey into research like?
I did my B. Tech in Biotechnology from Guru Gobind Singh Indraprastha University, Delhi following which, I completed my Ph.D. at JNCASR, Bangalore. Here, I started looking at how enzymes work focusing on their kinetic and catalytic mechanisms. However, towards the middle of my Ph.D., my work transitioned into metabolism. I was looking at how the malarial parasite Plasmodium falciparum rewires its metabolic network for successful invasion and how it succeeds in being parasitic in the human host. Our work showed that fumarate, an end product of the purine salvage pathway is recycled to aspartate and this happened through the TCA cycle. This cycle is now known as the fumarate cycle. It was also then that papers on cancer metabolism started coming out. Given my work and the way the field was taking shape, I became really interested in how metabolic state influences cellular physiology and pathophysiology.
It so happened that when I was looking for post-doctoral opportunities, I found this intriguing project at EMBL Heidelberg, which was to look at the metabolic regulation of mouse embryonic development. I thought this was a really unique and novel project because, at that point, most of the studies were done at pre-implantation stages, primarily with the motive to optimize in vitro fertilization techniques. But then, nothing was known about post-implantation stages. So I moved into studying it.
The first thing my Post Doctoral Advisor at EMBL, Alexander Aulehla showed me was this movie where Notch signalling pathway activity waves were sweeping across mouse embryonic presomitic mesoderm tissue. That moment is still in my memory. Coming from a biochemistry background and mostly dealing with western blots and bar graphs, looking at how signaling dynamics happen at the cellular level was really fascinating. This inspired me to develop a FRET-based sensor for pyruvate in collaboration with Carsten Schultz’s lab at EMBL, Heidelberg. Using FRET imaging and complementary approaches of MS metabolomics, we could show a glycolytic gradient across mouse embryonic PSM, which is critical for axis elongation. The fields of biochemistry and developmental biology are poles apart and merging both of them was a challenge, but I think at the end of it, it all came together. After that, I went to the Beatson Institute, Glasgow to gain some more expertise in mass spectrometry. I came back to India in 2020 to set up my research group at IISER Berhampur.
So how and why is the metabolic state dynamic in the developing embryo?
While the embryo as a whole requires primary nutrients for growth, our work shows that at the cellular level, the requirements for these nutrients vary. This is further strengthened by recent publications that show metabolic gradients exist in other morphogenetic fields as well as in the embryos. At present, we are trying to decipher the role of these metabolic gradients that exist across different regions of the embryo. It is known that diabetic pregnancies face a high risk of developing abnormalities in the embryo, and these abnormalities are very regional, like deformities in digit formation. Why such specific effects at a cellular level is still an open question. But now, with the discovery of these gradients, we hope that it’s probably due to certain regions of the embryo being affected more than others. Such small changes might be enough to put them out of sync in development, leading to these deformities. But further research is needed to investigate exactly how this happens.
And, how does the state of metabolism change in tumour cells?
A tumour is a heterogeneous mass of cells. The cells are all trying to compete with each other, and during rapid proliferation, some regions are deprived of blood vessels. These regions get very poor nutrition, and their metabolic state changes in order to survive. They take alternate nutrients, grow, and proliferate.
I suppose you also teach the BS-MS students. Do you teach biochemistry or developmental biology? Or both? And, how has it been maintaining a lab and also teaching an undergrad course?
I started with teaching biochemistry and developmental biology, but with more of my colleagues joining in, I currently teach only developmental biology. I’ve always enjoyed teaching right from my PhD days. Now, starting a lab has been an effort, especially because we are a new institute situated in a small city. There are multiple challenges, but one thing that has really helped me and my colleagues is having wonderful students. They bring in a lot of energy and passion because they’re still learning, and when you combine learning with actual research, their wonder is just amazing, and it’s very infectious. That really gives us the energy to move forward. For example, when I wanted to start this developmental project, the students who joined at that point said, “We don’t have a mouse system, so what is the alternative system?” I said, “People use chick embryos, but I don’t know where to get them.” So they themselves went out and asked the local vendors and did it all by themselves to establish the system. That is something that really pushed us to take up challenging projects. Of course, there are other issues we keep having, but we need some positive energy from somewhere, and we get that from the students.
And how has it been these last four years as a young PI?
While the pursuit of academic success is always on, my best moments of happiness are those when my students correct me while working with them. Apart from students, one of the positive aspects is the support from my peers. When you move from a postdoc to a PI position, suddenly, you see a big vacuum: “Where do I go?” As a postdoc, you can go to your postdoc supervisor. But as a PI, you need someone to talk to who has experienced your position and understands it. I’m very grateful to Sunil Laxman at InStem and Manish Jaiswal from TIFR Hyderabad who have been really helpful. Just talking with them is enough to de-stress.
Where do you want to see the devbio community five or ten years down the lane? What are some of the changes that you want to see in the community in India?
Typically during PhD interviews, I hear prospective students say that their research interest is either cancer or molecular biology, which are very broad fields. Very rarely does someone express a genuine interest in understanding how organisms develop. So, I think as a community we need to make students more aware of developmental biology and what the field is about at the undergraduate level in colleges and Universities.
With advancements in microscopy and labeling techniques, single-cell sequencing technologies, and the development of ex vivo systems like gastruloids, developmental biologists are now better equipped to ask questions at the cellular and sub-cellular scale. I expect the developmental biology community in India to excel in this domain through collaborative projects with cell biologists, physicists, and computational biologists.
Lastly, integration of this knowledge with fields of ecology and evolution is needed. At present there is a lack of collaborative efforts between molecular biologists and organismal biologists. I feel the dialogue needs to happen soon if we need a holistic picture of evolutionary drivers and constraints on the emergence and maintenance of developmental forms.
what do you do outside of your work? What are your hobbies?
Berhampur is a small city with nothing much to do after work. My friends in Bangalore tell me that it takes them about an hour or more to shuttle to work every day. I say, lucky you! It only takes me five minutes. So, these days—meaning from the last year or two—I have made it a point to read as much as possible outside the domain of science. This actually started during my postdoctoral time in Glasgow. I was staying in Edinburgh and had to take a train daily for about 45 minutes. During that time, I was reading fiction. It takes my mind away from the daily routine. I also tell my students about this and sometimes, students do pick up a book and we do an informal book club.
