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The shared world of Leishmania and us: A journey of adaptability and co-evolution

Debolina Manna

A childhood fascination with the image of a scientist led Budhaditya Mukherjee, an Assistant Professor at the Indian Institute of Technology Kharagpur (IIT Kharagpur) and an EMBO Global Investigator Network (EMBO GIN) awardee, to a career studying one of the world’s most adaptable parasites, Leishmania. In this profile, he reflects on research, resilience, mentorship, genome plasticity, and how understanding pathogen evolution may help address drug resistance and chronic infections.

Budha EMBO

Sometimes, minute incidents can profoundly shape a person’s dreams; similar to a tiny, blood-seeking sandfly whose bite can define the path of a microscopic parasite like Leishmania, causing it to adapt and survive in the liver and spleen of a human.

For Budhaditya Mukherjee, it was when he attended a lecture by one of his school alumni delivering a research talk at his school. I was in my seventh grade, and I heard him speak about radiophysics. Although more than science, the imagery of a scientist — intelligent, confident, ambitious, smart and knowledgeable — captivated me, and I wondered what it is like to be one. This one moment shaped the entire trajectory of my career and helped build my dreams”.

Now an Assistant Professor at the Indian Institute of Technology Kharagpur (IIT Kharagpur) and a member of the EMBO Global Investigator Network (GIN), he reflects on his journey and finds it interesting how much we humans have in common with the life of a parasite. Much as we try to embrace the good, neglect the bad, and adapt to adversities, Leishmania modulates its chromosomal patterns and genetic makeup through a phenomenon known as genome plasticity to achieve drug resistance.

He found the concept so fascinating that it emerged as the core theme of his lab, and his team now focuses on understanding host-parasite co-evolution using Leishmania as the model pathogen. Drug resistance in leishmaniasis has remained a persistent challenge; so they ask a simple but critical question: instead of eliminating the parasite, how does drug pressure sometimes make it fitter and better adapted to survive? Despite the withdrawal of older drugs like antimonials, resistant parasites continue to infect humans and resist newer therapies too — does Leishmanias genome plasticity make this possible?

Budhaditya Mukherjee with his PhD students during the initial years of the lab. (Left to right: Supratim Pradhan, Budhaditya Mukherjee, Ankita Mandal Mukherjee, Souradeepa Ghosh, Shatarupa Bhattacharya, Shubhangi Chakraborty, Debolina Manna)

Growing up, he defied the usual engineering vs medical” dilemma, and went on to pursue a BSc in Zoology and then MSc in Genetics. Amid a series of unplanned events, he eventually joined the lab of Syamal Roy at the CSIR-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata for his PhD. Budhaditya attributes this achievement to his parents, who never questioned his choices but rather supported whatever he wanted to study, and to his wife and best friend, Ankita, who, to him, is his pillar of success”.

However, the journey of a parasite that constantly struggles to survive the harsh conditions of the sandfly and the human immune system is as challenging as a human’s. When asked about his PhD experience at the lab of Syamal Roy at CSIR-IICB, he reminisced about how the dynamics of drug resistance in Leishmania always bothered him. 

As his initial proteomics-based research to decipher drug resistance failed to gain prominence, his side project on the anti-inflammatory molecule interleukin-10 (IL-10) response in Leishmania-infected immune cells gained traction. Eventually, his PhD research revealed that drug-resistant Leishmania parasites utilise host IL-10 to promote drug resistance, rendering the drugs ineffective for killing. His eagerness to know more about infection biology led him to the lab of Dominique Soldati-Favre at the University of Geneva, which significantly trained him in parasite cell biology and genome editing.

Having transitioned from bench to office, Budhaditya recognised substantial differences between being a mentor and a mentee. In his PhD, he was strongly encouraged to think critically and defend his ideas, but in a gentle, supportive way. While during his postdoctoral work, he was pushed through direct, probing questions, often without much cushioning. Apart from his work, the major challenge in his postdoctoral journey was the initial cultural transition in a completely new continent — I doubted myself more than I expected. There wasn’t a quick fix, just patience. Over time, adapting to a new environment, both scientifically and personally, became part of the learning process.” It was challenging, but it shaped his independence, precision, and resilience. That shift proved crucial in shaping his current research identity.

Was he adapting and becoming more resistant like Leishmania does in adverse situations? 

Contrary to the idea that the journey of a parasite is smooth, most of them actually die, and few emerge victorious. To counter the odds, some resort to manoeuvring human cells in a way that does not pose a threat to kill them. As a young scientist, Budhaditya had some compelling theories about how parasite factors can drive evolutionary changes in parasites’ adaptation. Despite his attempts, subtle suggestions to choose a more global and lethal pathogen like the malaria-causing Plasmodium, rather than Leishmania, frequently arose during his interviews or personal interactions. Eventually, his ideas found a home when he received the opportunity to build an independent research team at IIT Kharagpur.

As Budhaditya was almost set to start with his first two PhD scholars on board, they were unexpectedly hit by the COVID-19 pandemic. His lab — fundamentally based on wet-lab experiments — faced multiple challenges with delays, uncertainty and lack of resources. But gradually, through persistence and perseverance, the work started taking shape.

Adapting to changes and evolving together as a group has been key. In many ways, this co-evolution mirrors the very systems we study in the lab. I believe this has taught me a lot, not only about science but things beyond that.”

It is through both adversities and support that he transitioned from being a mentee to a mentor. Earlier during his supervision, he stayed closely involved with his PhD scholars, sharing failures and appreciating successes. Over time, he realised that each student is different, with unique motivations and goals.

The present members of Budhaditya Mukherjee’s lab. (Left to right: Shatarupa Bhattacharya, Sohini Mukherjee, Arkapriya Bhattacharya, Shubhangi Chakraborty, Ankita Mandal Mukherjee, Budhaditya Mukherjee, Riddhiman Dey, Nilanjan Pradhan, Debolina Manna, Chandana Dey, Deneshraj S, Sunandini Bhattacharya, Aparajita Pati)

The correlation between day-to-day experiences and scientific insights gave rise to another solid question in the lab — how adaptations influence where the parasite survives in the body. In conditions like post-kala-azar dermal leishmaniasis (PKDL), where parasites shift from internal visceral organs to the skin, creating long-term reservoirs for transmission, understanding what drives this change in their path or tropism” is critical. The lab gradually aims to move beyond a drug-centric view of resistance and uncover the broader principles of pathogen adaptability and co-evolution under drug and host pressure, which can combat chronic and relapsing, resistant infections in pathogens with high genome plasticity.

Being a part of the EMBO Global Investigator Network, he admires its vision, which aims to address the fundamental questions of biology, regardless of the kind of model one uses. The ability to exchange unpublished ideas and get feedback from peers and mentors, often outside his immediate field, has the potential to bring fresh perspectives to the questions still unanswered by his lab.

For a complex problem like pathogen adaptation, this kind of cross-disciplinary thinking is invaluable. He also agrees that access to training and advanced facilities is equally important. Many of the questions raised in the lab require technologies and expertise that are not readily available in the institute setting. Through EMBO GIN, his students can gain hands-on experience in cutting-edge approaches rather than relying solely on outsourcing, which is critical for long-term capacity building.

To him, the best part of being one among all in EMBO GIN is the visibility and platform it offers, especially for the students, to connect with the global scientific community. Leishmania is a neglected pathogen, and there are not too many labs that are trying to understand the evolution of drug resistance in this highly adapting parasite. He sees EMBO GIN as an ecosystem that will not only strengthen his current work but also shape how he and his students grow as a lab in the years ahead.

With such a wonderful global initiative giving him confidence, he also feels the necessity for the Indian scientific ecosystem to flourish more. Compared with when he first started as a new PI in India in 2019, he feels the research ecosystem has improved considerably. Initiatives like the Anusandhan National Research Foundation (ANRF) early-career grants have certainly helped, both in terms of increased funding and, importantly, more timely disbursement.

Now, as he slowly moves towards a more experienced phase of his journey as a scientist, he believes we should actively work towards making science more accessible, understandable, and meaningful to different audiences, even though we haven’t been traditionally trained to do so. In an era marked by advanced scientific technologies, misinformation seems to be rampant too, and it becomes the responsibility of the scientists to ensure clear and trustworthy communication with the broader public. He also thinks that effective communication is a two-way process, where it becomes equally important to engage with the general public to listen to their insights and incorporate them to develop scientific advancements for real-world application, and ensure that science remains accessible, trustworthy, and relevant to society.