Dr Nishith Gupta on Peter Hegemann, Optogenetics & Indian Science
For more than 15 years, Prof. Nishith Gupta has worked with Peter Hegemann, who shared this year’s Nobel Prize in Physiology or Medicine for optogenetics. Together they took the technique into infection research. Now a professor of biological sciences at BITS Pilani’s Hyderabad campus, where he founded the iPEARL research labs, Dr. Gupta spoke to Dr. Subramaniam Iyer, the Executive Editor of Neo Science Hub about the laureate, the prize, a parasite that lives inside our cells, and what Indian science needs.
You have worked with Peter Hegemann for many years. What is he like as a scientist?
If I had to describe Peter in three words, I would say brilliant, focused and straightforward. He is an incredible scientist to work with. Our association goes back more than 15 years, and I have learned a great deal. Every time I walked out of his office, I had learned something new, and much of what I learned there has stayed with me to this day.
Has he visited you in Hyderabad?
Not yet. When I moved to Hyderabad in 2021, Peter and I planned a focused meeting here on optogenetics, biosensors and mechano-optobiology. But those were the Covid years, and I was still settling in, so the plans did not go through. There is certainly still a plan for him to visit. What has happened instead is that I have visited Peter three or four times in the past five years, and many of my scholars have spent time working in his lab.
Are you still collaborating?
Yes, though not day to day. We communicate, and we have work ongoing. Peter is a formal collaboration partner on my current grant, a DBT/Wellcome Trust India Alliance Senior Fellowship. Before I moved here, we also held two joint grants from the German Research Foundation. So the connection is strong, and we still share many thoughts and ideas. The interaction cannot be very frequent, because he is very busy, but whenever I write to him, he responds.
In simple terms, what is optogenetics?
The technology is still new, and not many people work on it in India, so I understand that optogenetics still has to make headway here. If I had to explain it to my children, I would say this: you engineer a cell or an organism so that it responds to a light trigger, light of a particular wavelength. You can then switch certain pathways in the cell on and off, and look at what that cell or organism does. All of it is controlled by light. That precision is exactly what makes the technology so useful.
Georg Nagel, one of the laureates, said the prize came too early. What is your view?
There is a committee that decides; it deliberates, and everything remains confidential. I agree that there are many technologies, and many people, who deserve the same honour: T-cell therapies, vaccines, the new GLP-1 drugs such as semaglutide. All of them deserve recognition.
But optogenetics has been around for more than 20 years now. It has been expanding gradually, making its way into different disciplines, and it holds enormous potential. Obviously I cannot look into the committee’s mind, but I think the committee sometimes recognises the potential a technology holds, and that such a technology deserves recognition. In that sense, optogenetics certainly qualifies for this honour.
And it has been a long wait, I must say. My personal feeling, from working with Peter, is that the process has been going on for the last ten years. If anything, I would say it came a bit late.
Where does India stand in optogenetics?
Honestly, not many people are working on it. We are among the first. I know of two or three labs, and one of them belongs to my friend Suneel Kateriya at Jawaharlal Nehru University. He worked with Peter in the early days and was involved in the original work that eventually received the Nobel Prize. He set up his lab in India long before I came back, and he has been studying optogenetic proteins.
What we did was pioneer the application of optogenetics in a totally new discipline, infection research, together with Peter. There may be others working on it in India whom I do not know of. But all in all, the field is still at a very nascent stage in our country.
How is it to be back in India after so many years abroad?
I am asked that very often. I do not regret coming back. The decision took time to make, but once it was made, it turned out to be a very good one for us. Most of what I had planned, I have been able to achieve, and we have been able to implement the vision I had. So, no regrets.
How do you see Indian funding for basic science?
Personally, I have not had any difficulty getting funds. We have been very well funded by many government agencies, apart from the DBT/Wellcome Trust funding. But I do see that the country is investing heavily in innovation and in need-based priority areas, which makes most of our funding translational. I feel funding agencies could provide more for foundational and basic research, because that is where inventions come from. So, apart from investing in innovation, I would like to see more invested in invention.
From Shahjahanpur to Leipzig to Hyderabad: how has the journey been?
I have been fascinated by visiting places since I was a child, though I never had the opportunity then. I still remember Raj Kapoor’s film Around the World, the story of travelling the world on eight dollars. It is one of the most inspiring films I remember from childhood, and it may have been the trigger: to see different places, to meet different people and cultures, to learn their history.
In science, one decision was critical. Growing up in India, the Indian Institute of Science holds great value for young aspirants, and it did for me. I wanted to do my PhD there, and fortunately I got admission. In parallel, I received an offer from the University of Leipzig in Germany. It was a tough decision, but I made it, and that was the turning point. Once the choice was made, there was no looking back. There was a lot to explore and a lot to learn, and that took me to different places. At some point I felt I should come back. There are many opportunities here, and I wanted to give something back to our country and invest where I see a lot of potential.
What is Toxoplasma, and why does it fascinate you?
It is a truly fascinating parasite. I am not a parasitologist by training. My PhD was in microbiology and biochemistry, on an environmental biotechnology project. I first came across Toxoplasma during my postdoctoral work with Professor Dennis Voelker in Denver. Over time I became fascinated, partly because you can do so much science with it. It is one of the best model pathogens: it invades cells and manipulates them in ways that fascinate the scientists who work on it.
Toxoplasma is a single-celled eukaryotic organism. It has all the machinery that our own cells have, and it lives inside host cells. That is the most interesting aspect: one eukaryotic cell living inside another. It drew me to the question of how a pathogen and its host interact. How does the parasite communicate? How does the host cell communicate? Understanding that tells us about the basic concepts of parasitism. The parasite has a lot to teach us.
You have foundediPEARL and VAMPIRE. What are they?
Thank you for recognising those initiatives. We have several more, but iPEARL was one of the first: a centre for advanced research that could become a unique entity. It does basic and translational research, but it also takes a holistic approach to training scholars, and it includes educational and communication outreach and international exchange. We packed all of this into one concept. The aim has always been to become an international role-model lab, and we, and our scholars, are working very hard to make that happen.
How do you spot talent among young Indian scientists?
Talent is everywhere; it depends on how you look. It all comes down to how we select individuals. I do not always go by academic merit. You have to meet people and understand what they want to achieve. We need individuals who are highly focused, and I understand that today it is not easy to find people who are not distracted or diluted by the many opportunities around them. So it takes a few rounds of conversation to really know a person and what they want to achieve, and that goes into our selection.
The malaria parasite is a close relative of Toxoplasma. How should we fight it?
I am not a malaria biologist, although the malaria parasite is very similar to Toxoplasma, so I cannot claim expertise. But funding agencies have invested a great deal in research, and malaria cases are coming down. For now, the main approaches remain drugs and vaccines, and scientists across the world are working on both. It is mostly a problem in tropical settings, but a lot of research also happens in Western countries. My expectation is that over the next five years or so, cases will go down further, and eventually we will eliminate the disease.
Parasites are tiny yet complex. How far can science go in understanding them?
There is a great deal to do. There are millions of parasites, and we do not yet know all that diversity. We work with a few model pathogens; ours is Toxoplasma. What has always fascinated me is the communication between a parasite and the host cell it lives in, and we know very little about it. With improving technologies, including optogenetics, we now have a way to address that molecular communication between the two. If funding is sustained and new technologies keep emerging, we should be able to answer challenging questions that could not be addressed before.
What does the research landscape look like from your lab?
As a lab, we are doing well. Our scholars put in a lot of effort, the facilities are good, the institute is very supportive and the funding agencies have been great. What matters most is finding the right question and the right way to answer it, and that is where people should invest more. Which questions make us more competitive? Which questions solve global problems? Which help us collaborate with disciplines we had not thought of?
We are doing our share, and working hard to internationalise Indian science as much as possible. Every one of our doctoral scholars is required to spend time in partner labs overseas. They learn new technologies, bring them home and establish them here; they also learn new cultures and make new friends. If we can inspire the younger generation this way, I believe that is the right approach to mentorship.
What initiatives are you taking to build the science ecosystem?
Now that iPEARL is up and running, we are starting new initiatives. One is educational outreach to schools, because I feel there is a major gap in how children perceive and learn science. If we can offer students in grades 9 to 12 a more practical approach, starting with biology, the discipline we understand best, I hope they will learn to ask the right questions. We are launching this in Hyderabad and the broader Telangana and Andhra Pradesh region. The second is internationalising India’s scientific landscape. There are many ways to do that; I am working on a series of articles and new approaches, and we are looking for the right platform to communicate them.
Many young people are drawn to applied fields such as IT. What would you tell them about core science?
It is easy to think about the present. People see a problem, and the first thing that comes to mind is how to solve it. That often means repurposing a technology or a resource for a new context, and that is innovation. Many scientists work on those principles. But it is much harder to think about something that may not get recognition, traction or appreciation today, yet could change the world 50 years from now. Most people think within their own lifetime.
Here is an example. In a class the other day, we discussed an optogenetic technology applied in plants. Scientists expressed a light-regulated protein in the guard cells of the stomata, the tiny pores through which plants exchange gases, so that the stomata could close very quickly in response to light. That could reduce water loss in strong sunlight. A student asked me what its application was today. I said there were enough applications to fill the whole lecture, but that the real question is what this technology could change 10, 20, 30 or 40 years from now. That is how you should be thinking.
Much of what we see today is not new work. It began 50 or 100 years ago. Optogenetics did not happen only in the last 20 or 25 years. People have watched pond algae for thousands of years, and scientists have studied how algae move towards light for at least a century. Peter Hegemann himself was working on it in the 1980s. The genesis of optogenetics goes back a long way, to a time when nobody appreciated it. Think of CRISPR, which received the Nobel Prize a few years ago. It came from studying how bacteria fight off viruses: bacterial immunity. While everyone worried about their own immunity, scientists in a corner were asking how a bacterium defends itself against a virus. Twenty years ago, that was the most boring thing imaginable. The Nobel Prize typically goes to people who studied some of the most boring, ignored and dismissed things in the world. They do it because they enjoy it and want to satisfy their curiosity, not because of an immediate application. And then, 50 years later, something happens that turns everything upside down.
