At the Intersection of Physics and Biology: Tamal Das on Forces, Cells, and Curiosity

SH: Welcome, sir, to InScight. I am Suman Halder, your host for the day. To start, could you please introduce yourself and tell us about your current role at TIFR?

TD: At TIFR, our lab works primarily in cell biology with an interest in developmental biology. We study biological problems from an interdisciplinary perspective, looking at biophysical aspects such as extracellular matrix (ECM) tension, cell–cell forces, and the physical state and geometry of cells. These are areas a typical molecular biologist may not focus on, but they complement conventional molecular signaling studies.

Our main focus is on the collective dynamics of epithelial cells—where many cells behave as a single unit. Epithelial tissue, which forms protective coverings like the skin, and lines organs such as the gastrointestinal tract, kidneys, and lungs, is ideal for studying such collective behavior. These cells are tightly connected, so any activity by one cell involves coordination with its neighbors.

Epithelial cells are also under constant tension, attached both to neighboring cells and to the ECM, somewhat like a “cellular Spider-Man” pulling on its surroundings. This allows us to measure forces and understand how they support collective behavior. Alongside this biophysical view, we also study how organelles—such as mitochondria, lysosomes, the endoplasmic reticulum, and the nucleus—change in relation to tissue-level behaviors. In short, we connect processes inside a cell to tissue-level phenomena through force transmission and molecular signaling.

SH: So, you are mainly working experimentally?

TD: Yes, we are primarily an experimental lab. However, we also analyze our data computationally. For example, in studying nuclear dynamics, we track fluctuations in the nucleus and use Fourier analysis to examine their decay across spatial frequencies. While we do not perform simulations ourselves, we collaborate with soft matter physicists who handle modeling, while we focus on experiments.

SH: For the benefit of our readers, could you explain what TIFR is and its role in India’s research ecosystem?

TD: TIFR Hyderabad has a unique structure—there are no departments. Physicists, chemists, and biologists work under one umbrella, which promotes interdisciplinary collaboration. For students, this means great flexibility: even if they join through the biology board, they can work in any lab, including those focused on simulations or molecular dynamics.

This structure avoids pigeonholing researchers into narrow categories and encourages cross-disciplinary culture, which is rare in India.

Another key point is our focus on fundamental research. Many modern applications—like lasers—originated from purely fundamental scientific questions. Lasers, now an applied technology, began with the simple idea of collimating light, backed by theory long before practical use emerged.

While translational research is essential and rightly receives funding to directly benefit society, it should not come at the cost of fundamental science. TIFR’s mandate is to lead in fundamental research, ensuring that breakthroughs can later fuel impactful applications. Without such foundational work, progress in applied research would be only incremental.

SH: Now, can you tell us about some of the projects you are currently leading at TIFR and their broader impact?

TD: As I mentioned earlier, our lab focuses on the collective dynamics of epithelial cells. We have two broad objectives:

First, to test how much of what we read in textbooks truly holds in real biological systems and whether there’s more beyond those established ideas. For instance, we are studying how cells behave under dynamic situations such as during migration or when the tissue removes a harmful, mutated cell.

Within a cell, there are organelles—like the endoplasmic reticulum, Golgi complex, mitochondria, and the nucleus. A basic biology textbook will tell you their primary functions: the endoplasmic reticulum in protein synthesis, mitochondria as the “powerhouse” of the cell, and so on. But we are discovering that beyond these canonical roles, these organelles are also involved in signaling processes that help coordinate such dynamic events.

One specific project in our lab examines how “good” cells in the body identify and eliminate potentially cancerous cells. This is a vital, ongoing process—mutations occur continuously due to random errors, UV exposure, or toxic chemicals, and the body must constantly remove these faulty cells to maintain health. Understanding this could contribute to cancer prevention strategies.

Another line of research looks at wound healing. When there’s a gap or injury in epithelial tissue, cells migrate to close it. If we understand the exact mechanisms of how they do this, we might be able to design better wound-healing approaches.

So, on one hand, our work addresses fundamental biological questions like how intracellular structures influence collective cell behavior. On the other hand, it has potential applications in health and medicine, including cancer prevention and tissue repair.

SH: Could you briefly describe your academic journey, starting from your school years?

TD: I am from West Bengal and grew up in Howrah, where I studied at Howrah Zilla School. After Class 12, I joined IIT Kharagpur for an Integrated B.Tech–M.Tech in Biotechnology and Biochemical Engineering. I never attempted medical entrance exams; I was focused on engineering and initially aspired to be a physicist.

During IIT JEE counselling, I was curious about research opportunities. I asked what field had good prospects, and was told biotechnology was “the next big thing.” That’s how I entered the field.

I always had an inclination towards research. In my third year, a friend introduced me to Professor Suman Chakraborty from the Mechanical Engineering Department (now the Director of IIT Kharagpur). He was simulating DNA hybridization in a microchannel and needed input on the biological aspects. I joined him as a side project, and his intellect and mentorship inspired me.

Eventually, I pursued a PhD under his co-supervision, alongwith Prof. Tapas Maity from the Biotechnology department. This gave me the unique experience of working in two labs: the biochemistry lab in biotechnology and the microfluidics lab in mechanical engineering.

Professor Chakraborty’s physicist’s mindset influenced my thinking profoundly. For example, when I described a cell as having cytosol inside and media outside, he immediately framed it as a “two-fluid problem” and asked about interfacial tension—concepts rarely addressed in standard biology courses.

My PhD focused on bio-microfluidics, particularly how cells behave when confined in channels with heights comparable to the cell’s own height. I studied two main effects: high shear stress from fluid flow, and local concentration buildup from secreted factors.

After my PhD, I did a short postdoc (10 months) at the Institute for Cancer in Montreal, affiliated with the University Hospital of Montreal. There, I worked on ovarian cancer, designing microfluidic channels to trap spheroids—spherical aggregates of cancer cells—from patients. We tested different chemotherapy combinations on these “mini-tumors” to predict which regimen would work best for each patient.

Although impactful, I wanted to return to more fundamental research. I joined the Max Planck Institute for Intelligent Systems in Germany, in Joachim Spatz’s lab, initially proposing to study collective migration of cells in confined microenvironments. Ironically, in the next five years, I never touched microfluidics again.

This shift was deliberate. I often advise PhD students to identify their core niche and avoid staying too close to their doctoral topic out of comfort. Many researchers continue their PhD work as faculty, which is safe but can limit innovation. I decided to move towards biology, bringing in my physics and fluid mechanics background, rather than competing directly with established experts in microfluidics.

At that time, microfluidics research had two main tracks: Either you choose the pathway where theoretical fluid mechanics is applied to microfluidic systems, requiring deep expertise and mastery of the field. Or, you choose the track where Sophisticated multi-layer microfluidic “lab-on-a-chip” devices are used, which demand major infrastructure only a few institutes possess.

I realized I couldn’t compete in the first area and didn’t want my work to be restricted by the facility-intensive nature of the second. Staying in microfluidics risked producing only incremental progress, so I chose to focus on biology.

Joachim’s lab was the perfect environment—over 100 people, immense resources, and cutting-edge equipment. I decided this was my chance to redefine my career. I began focusing more on biological problems and less on engineering. This led to a discovery involving the protein Merlin, which plays a role in coordinating collectively migrating cells. That work was eventually published in Nature Cell Biology in 2015, and it has been central to my subsequent research objectives.

That transition from engineering to biology was challenging but rewarding. While I still value physics deeply, I recognize my own limitations in it. I collaborate with physicists for simulations and modeling, while I focus on designing the most precise experiments possible—a key responsibility for any experimentalist.

This is my niche: bridging biology and physics, maintaining collaborations across disciplines, and using my interdisciplinary background to ask unique research questions.

SH: So can you mention your collaborators also? And they are mostly biophysicists?

TD: Yeah, so the person right now with whom I am collaborating most, I mean from the physics side. It is Max Bi. He is at Northeastern University. So Max is my collaborator for many projects as such. We have projects related to the cell competition and also morphogenesis, we are currently working on 3–4 projects. My group and Max’s group are working.

Then I have collaborated and also collaborated with a mathematician in the University of Birmingham, Fabian Spiel. We have a work in #link(“https://www.nature.com/articles/s41556-025-01729-3”)[#underline[Nature Cell Biology]], where we looked at what endoplasmic reticulum morphology, how it undergoes the morphological changes during the wound healing and so. And Fabian provided a physical explanation underlying the morphological changes. It turns out that certain endoplasmic reticulum structures are energetically more favorable in one configuration than the other configuration. Within India, I have collaborated with two people.

One is Mohit Jolly, who is a Systems Biologist at IISc. We have so far collaborated in one project, but I wish to collaborate with him going ahead. And then within the institute, there is Saroj Nandi, who works on jamming and active matter.

SH: It has been quite a while since you completed your PhD. In your view, how has the experience of conducting doctoral research changed since then?

TD: Some things about a PhD never change—one of the most important is working with smart people. I’ve been fortunate to work with several, starting with Professor Suman Chakraborty.

He has an exceptional ability to grasp concepts in new fields at remarkable speed, draw analogies from other areas, and import those ideas effectively.

My postdoctoral advisor, Joachim Spat, was another influence—deeply insightful, with a clear vision for where science is heading.

One thing Professor Chakraborty told me has stayed with me: you only realize how good your PhD was about 10 years after finishing it. The real measure is what you are doing a decade later, because a PhD’s value lies in the skills and judgment it gives you, not just the techniques you learn.

For me, one of those key skills is the ability to distinguish good science from bad—ordinary research from extraordinary. At the start of a PhD, you’re naïve: you read a paper and get excited without fully understanding the context or significance. Over time, you should learn how to filter, to see what’s worth pursuing.

This filtering skill has become more important because of how research has changed. My PhD years (2006–2010) were pre-social media for science. We had internet access, but slower, and less information bombardment. I still visited the IIT Kharagpur library to browse journals. Today, with platforms like Twitter, I can see research updates from across the world instantly—but this flood of information makes it harder to focus.

Earlier, the challenge was getting information; now, it’s filtering it. You can realistically read at most a paper a day, so you have to choose wisely.

Another lesson from my PhD is the value of patience when chasing a big scientific story. It’s tempting to split findings into smaller publishable parts for quick output. But if you want a complete, mechanistic, and impactful narrative—from first discovery to underlying process—you must invest years.

SH: What emerging trends in biotechnology are you most excited about?

TD: One area I find particularly exciting is synthetic biology, which sits at the interface of biology and chemistry. Different people define it differently. For example, in iGEM competitions, teams design synthetic genomes. In Europe, my postdoc advisor Joachim is involved in a large project called SynCell, where they build artificial vesicles and add components step-by-step to determine the minimal composition needed for them to behave like cells.

My own interest lies in programming the internal structure of cells or even entire tissues to control their morphogenesis. This is something we haven’t started yet, but I’m eager to explore it.

Another growing area is the integration of biophysics and principles of physics of matter into biology. Mechanobiology has been developing for over a decade now, so it’s not entirely new, but synthetic biology remains the most exciting frontier for me.

SH: You’ve worked as a scientist in multiple countries. How would you compare the research cultures and professional norms in these different environments?

TD: I’ve worked in India, Canada, and Europe.

In North America, research is very grant-driven. PIs are constantly writing proposals, and that pressure is passed down to students. You’re pushed hard - sometimes it’s “swim or drown.”

In Europe, the pace is calmer. This works well if you’re self-driven, as I was, but it can also lead to complacency. Some people settle into technical positions without ever returning to the pressures of academia. Institutions like the Max Planck Society offer vast resources, but it’s easy to get comfortable.

In India, the culture is somewhere in between. At top institutes like TIFR and IISc, we’re doing fine, but pressure and resources vary widely.

SH: Have you had any experience working in industry? How do skills and expectations compare with academia?

TD: Not directly. My only exposure came during my PhD at IIT, which has strong industry links. While working on microfluidic systems, I collected data on how surface roughness affects fluid flow and heat dissipation, which was valuable for a chip-making company.

Their problem was cooling increasingly small semiconductor chips, which generate more heat. My findings on heat and mass transfer proved useful for their designs. That was my only real taste of industry collaboration. Other than that, I can’t recall any other.

SH: In recent times, PhD graduates in India are facing a shortage of career opportunities. What can be done at the institutional level to address this?

TD: This is a difficult question, and I have two perspectives. The common answer is, of course, to create more institutes. But I believe PhD students themselves need to be proactive. Before starting a PhD, survey the available opportunities and ask whether you are exploring all possible career paths or narrowing yourself into a niche. The more niche your research, the fewer options you’ll have.

For example, my first PhD student always wanted to work in industry. I advised her to do a postdoc in a city with many startups — places like Boston, the Bay Area, Paris, Frankfurt, or Singapore — and ideally in a lab collaborating with those startups. In India, much of the industry is still service-oriented rather than innovation-driven, which limits opportunities for scientists. This is especially true in biology and biotechnology, though pharma does slightly better, mainly hiring chemists.

Many people treat a PhD as just the next step after an MSc, without considering the reality that science, like sports or the arts, is a creative field with very few top positions. In cricket, for example, countless people play at the club level, but only a handful make it to the national team — the same applies to research. The government could expand funding and facilities, but there will always be limits. Students should be aware of these constraints and be open to alternative career paths.

SH: As a working experimental biologist in India, what barriers do you face in your research compared to other countries?

TD: Rules and regulations can slow things down, especially procurement. The “lowest bidder” rule in tenders is meant to prevent financial wrongdoing, but it can also delay essential purchases. That said, things have improved a lot. During my PhD at IIT Kharagpur, ordering chemicals could take months. At TIFR Hyderabad, purchase orders are processed in a week’s time, and common chemicals often arrive within days, similar to my experience at the Max Planck Institute.

Also, where you work matters. At TIFR, all PhD positions are funded by the institute through the Department of Atomic Energy, so I don’t have to secure individual grants to pay students during their regular tenure. In most Western institutions, PIs must fund their students through grants, and without one, the student may have to leave. Both systems have advantages and disadvantages, and you need to understand how to work within them.

SH: Sir, I want to shift the topic of our discussion a bit and just ask you about this, that biophysics is at the interface of biology and physics. So, how do you see the future of this field evolving and also, will artificial intelligence become like an indispensable tool for a researcher in this field?

TD: Yes, in many ways I believe AI - especially large language models (LLMs) like ChatGPT and Google Gemini - has made my work faster and more convenient. Until recently, I was the one writing most of the analysis codes in my lab, as many of my students come from biology or biochemistry backgrounds.

Previously, if a student gave me data and asked for a custom analysis script, I knew exactly what to do but struggled to find a continuous block of time to start from scratch. It could take months before I finally sat down to code. Now, I can ask an LLM to draft a basic version in MATLAB, then quickly refine it myself—allowing me to respond to students much faster.

For literature surveys, AI-based tools like Undermine AI and ChatGPT’s research mode can quickly gather relevant papers and even give preliminary interpretations. Of course, these outputs must be verified, as AI sometimes generates incorrect or fictitious references. Still, it feels like interacting with a knowledgeable collaborator who speeds up the initial stages of research.

AI has also transformed image analysis. Ten to fifteen years ago, segmenting cells in tissue images was challenging without high-quality images, and standard algorithms like watershed had clear limitations. Now, tools like CellPose, trained on millions of examples, can match human-level segmentation accuracy.

A growing frontier is integrating multimodal datasets—combining imaging data, transcriptomic or genomic sequences, and medical imaging such as MRI—to build better predictive models. In physics, similar AI approaches are being used to tackle previously intractable problems.

The real question, however, is about AI’s limits: distinguishing between automated analysis and genuine scientific insight. For instance, debates continue over whether AlphaFold’s success is itself a discovery or merely a powerful tool enabling further discoveries. Regardless, I view these technologies as disruptive—in the positive sense—because they fundamentally change how we approach scientific problems.

SH: Despite the large number of students in our country, it often seems that the research output being generated from here is not the highest quality compared to the other countries like US and Europe and what do you think is the system we are using for this? So, that doesn’t depend, in my opinion, on the business.

TD: It largely depends on the PI. While it’s true that overall research output in India may lag behind some countries, there are many scientists here—physicists, biologists, chemists—whose work matches the best being done abroad. In my own lab, we have a couple of strong results coming out soon that, to my knowledge, no one else has achieved in our field.

The challenge is that the proportion of such high-performing researchers is small, and this is linked to funding. If a country spends 4% of its GDP on research and another spends only 0.4%, the difference will be visible in facilities, opportunities, and output. Of course, the relationship isn’t perfectly linear, but resources matter.

That said, the quality of PhD students in India is on par with those abroad in terms of intelligence and capability. Many top labs in the US and Europe have a large proportion of Indian and Chinese researchers. The difference often comes down to vision. PIs abroad tend to be more ambitious, while funding constraints remain a persistent limitation here.

Your career path depends on your interests, but whatever your field - physics, chemistry, biology, mathematics - ensure that the questions you pursue are at the forefront of that discipline. Incremental questions will yield incremental answers. Aim for bold, high - impact problems. For example, instead of testing how a known reaction behaves with a slightly different salt concentration, consider introducing a completely novel element—such as a rare-earth salt—and exploring its entirely new interactions.

To reach that level, develop a regular habit of reading top journals in your field, even outside your immediate research area. Focus not on impact factors but on how influential work is structured and executed.

Attend high-quality conferences where the leaders in your field present. Listen carefully, engage with them if possible, and understand the direction in which the field is moving. This is a lifelong process—even as a PI, I still attend key meetings to track emerging areas and identify promising research directions.

SH: Thank you sir. It was my pleasure to have this chance to interview you.