The Nobel citation names a light-gated channel. The Hyderabad story runs on a different idea from the same Berlin laboratory: light that makes a cell’s own chemical messages. Inside the long partnership between Nishith Gupta and Peter Hegemann.
Toxoplasma gondii has no use for light. It lives inside other cells, out of sight, in almost any warm-blooded animal it can reach, people included. Yet for more than a decade, strains of this parasite have been engineered to answer a flash of blue light, first in Berlin and now in Hyderabad.
The tool that makes this possible came out of Peter Hegemann’s laboratory at Humboldt University. On 5 October he shared the Nobel Prize in Physiology or Medicine with Georg Nagel and Karl Deisseroth. The scientist who first put that tool inside the parasite is Nishith Gupta, now a professor of biological sciences at BITS Pilani’s Hyderabad campus.
Most reports this month have joined the two men under the broad heading of optogenetics. That is accurate, but it misses the interesting part. The Nobel Committee honoured discoveries concerning light-gated ion channels. The work Gupta and Hegemann did together used something else from Hegemann’s toolbox: light-activated enzymes. To see why that matters, you have to start with what a parasite listens to.
A switch for chemistry, not voltage
Channelrhodopsin, the protein at the heart of this year’s prize, is a pore. Light opens it, charged ions rush through, and a neuron fires. That suits nerve cells, which do their business in electrical pulses lasting thousandths of a second. Gupta himself put the advantage plainly to reporters after the announcement: light can drive one chosen type of neuron within milliseconds, whereas electrodes and drugs act on many cells at once.
A parasite does not think in voltage. Its big decisions, when to invade a cell, when to glide away, when to go quiet, are carried by small messenger molecules, chiefly cAMP and cGMP. Enzymes called cyclases make them; other enzymes called phosphodiesterases destroy them. Control the messenger and you control the decision.
Hegemann’s group had been looking for light-sensitive versions of those enzymes. In 2011, with Nagel among the co-authors, his team described bPAC, a small photoactivated adenylyl cyclase from Beggiatoa, a bacterium of sulphurous mud. Shine blue light on bPAC and it makes cAMP; switch the light off and it stops. A second tool, a rhodopsin fused to a guanylyl cyclase and known in the trade as RhoGC, does the same for cGMP.
These are not the molecules the Nobel citation names. They are their cousins: optogenetics turned from a way of firing neurons into a way of writing a cell’s chemistry with light. Hyderabad’s connection to the prize runs through these cousins.
One parasite, two lives
Toxoplasma leads a double life. In its fast form, the tachyzoite, it multiplies quickly and kills the tissue it occupies. Under immune or chemical stress it changes into the bradyzoite, a dormant form that walls itself into cysts and can stay in the host for life. What tells it to make that switch has long been a central question in the field.
The obvious experiment had a flaw. Drugs that raise cAMP raise it everywhere, in the parasite and in the human cell around it. Nobody could tell whose cAMP was doing the work.
Gupta’s answer, published in the Journal of Biological Chemistry in 2013 with Hegemann as a co-author, was to build bPAC into the parasite itself. Now a pulse of light raised cAMP inside Toxoplasma alone, on cue, in parasites inside or outside host cells. The result was clean: the parasite’s own cAMP turned out to be needed for invading host cells and for the change from one stage to the other. The authors noted, almost in passing, that the same trick should work in any pair of organisms living one inside the other, whether symbiont or pathogen.
Germany’s research council, the DFG, then funded Gupta from 2015 to 2019 to take the idea further, with Hegemann named on the project. The plan was to raise cGMP with light as well, and to lower both messengers with light-controlled phosphodiesterases: the brake as well as the accelerator.
A protein the size of a small factory
The light switches were means to an end. The end was a map of how the parasite makes and breaks its messengers, and the map turned up oddities.
In 2019, in Life Science Alliance, Gupta’s group described the parasite’s only guanylate cyclase, the enzyme that makes cGMP. It is enormous: 4,367 amino acids, a molecular weight of about 477 kilodaltons, and 22 helices threading through the cell membrane. Bolted to the cyclase is a second machine, a P-type ATPase of the kind that pumps or flips molecules across membranes. The protein sits at the parasite’s front end and is essential for gliding, for breaking out of a host cell and for invading the next. One of the four authors, Ulrike Scheib, came from Hegemann’s department of experimental biophysics; the doctoral thesis behind the paper also used the light-driven RhoGC to raise cGMP in the parasite at will.
Then came the brakes. An earlier survey had found 18 phosphodiesterases in the Toxoplasma genome, 11 of them active in the fast-growing stage. A 2022 study, with Hegemann again among the authors, showed that ten of these break down both cAMP and cGMP, an unexpected looseness of design. Several differ markedly from their human counterparts.
That last point is where basic science starts to touch medicine. An enzyme the parasite needs, built differently from ours, is what drug designers look for. Toxoplasma is also a close relative of Plasmodium, the malaria parasite, so lessons travel.
From Shahjahanpur to Berlin to Hyderabad
Gupta’s route to the partnership was long. Born in Shahjahanpur in Uttar Pradesh, he took a master’s in biotechnology at Banaras Hindu University and a doctorate in biochemistry at Leipzig. After NIH-funded postdoctoral training at National Jewish in Denver, he set up his own research group at Humboldt University in Berlin, where he also earned the habilitation and the Venia Legendi, Germany’s formal licence to teach at a university. German parasitologists awarded him the Carl-Asmund Rudolphi Medal, the Robert Koch Foundation gave him its Young Scientist Award in Microbiology, and the DFG made him a Heisenberg Fellow.
The geography mattered. Gupta’s parasitology group and Hegemann’s biophysics department sat in the same Institute of Biology at Humboldt. Collaborations that last are often built on that kind of nearness: a shared seminar room, a student who can walk between two labs. Berlin gave him other neighbours too, among them an affiliation with the Max Planck Institute for Infection Biology.
Gupta came to BITS Pilani in Hyderabad as Professor of Biological Sciences and a Wellcome Trust–DBT India Alliance Senior Fellow, and has served as head of the department. There he built the Intracellular Parasite Education and Research Labs, iPEARL, with support from the India Alliance, the Department of Biotechnology and the institute. The lab works on Toxoplasma, Plasmodium and Eimeria, a poultry parasite, under a One Health banner that treats human and animal infection as one problem.
Asked to sum up his career on his own profile, Gupta puts mentoring first. By his count, more than 30 doctoral scholars, over 15 postdoctoral fellows and more than 50 undergraduate and master’s students have trained with him. Some of them are the reason the Berlin link outlived his move.
The Berlin thread did not snap with the move. Özlem Günay-Esiyok, who did her doctorate in Gupta’s group, went on to co-supervise projects with Hegemann in Berlin. One 2023 project offered to students paired bPAC and RhoGC with parasite ion channels, tested by patch-clamp in frog eggs and neurons, bringing the work full circle to Hegemann’s own home ground of channels. iPEARL’s own posts describe a researcher from the lab training in Hegemann’s laboratory in optogenetic tools and single-cell patch-clamping.
What the prize changes
Nobel citations are narrow by design. This one rewards a pore found in a pond alga and the act of turning it into a switch for neurons. But the laboratories that found it did not stop at the pore. They went looking for every way light could reach into a cell, and some of those ways ended up in a parasite that never sees daylight.
India has more than one tie to this story. DNA India has reported that Suneel Kateriya, now at Jawaharlal Nehru University, identified channelrhodopsin genes in algae while working in Germany in 2001. Gupta’s link is of a different kind: not a contribution to the prize-winning discovery, but more than a decade of joint work that carried its methods into infection biology, and a lab in Hyderabad where that work continues.
There is a modest lesson for Indian science policy in all this. The partnership was not created by a memorandum of understanding. It grew from years in the same institute, a German research council willing to fund an odd idea, and people who kept moving between Berlin and Hyderabad after the papers were out. Prizes cannot be planned. The conditions under which such partnerships grow can be.
In a lab on the outskirts of Hyderabad, a dish of parasites can still be told, with a pulse of blue light, to start a chemical conversation it would otherwise have started in its own time. The man who first taught it to do that now has a Nobel laureate as a long-time co-author. For Hyderabad, that is a better story than a medal.
Rashmi Kumari
Nishith Gupta is Professor of Biological Sciences and a Wellcome Trust–DBT India Alliance Senior Fellow at BITS Pilani, Hyderabad Campus, where he founded iPEARL and the VAMPIRE One Health initiative. He has also held affiliations with SickKids Hospital in Toronto, the Chinese Academy of Sciences as a President’s International Fellow, and Osaka University.
