Quantitative biology: Where physics meets feathers

From the theory of evolution to the more recent discoveries of antibiotics and DNA structures, our understanding of biology has revealed many of the mysteries of the natural world. However, it has also underlined how little we know about the early stages of animal life and precisely how an embryo creates bones and teeth, feathers or fur.

The missing pieces to this biological jigsaw have become a professional challenge for Arghyadip Mukherjee, the Junior Research Chair at QBio, a quantitative biology center created by ENS-PSL at the futuristic PariSanté Campus. “I work on biological problems – essentially on the development of animals – as a theoretical physicist, and I look for physical phenomena that play a key role as those animals develop,” he explains.

His fascination with both science and nature dates back to his boyhood in Asansol, India. With a physics professor for a father and a librarian for a mother, his aptitude for numbers and order was hardly a surprise. “At school, the thing I most wanted to do was to play cricket,” he admits. “But the subject that came naturally to me was mathematics, which later made me interested in physics. The thing is, I never saw these as boring subjects because, every once in a while, my father would tell us about how something had been discovered, and there was a sense of thrill and adventure about it.”

National recognition

By the time he was 17, Arghyadip was recognized as one of India’s most promising students, securing a prestigious KVPY Fellowship and the accompanying stipend for studies in his own country. However, after a bachelor’s degree at the Indian Institute of Science, the desire to experience a different culture took him to Germany and a PhD at Dresden’s Max Planck Institute, with the degree granted by the Technische Universität Dresden. After his work in Germany, which included a dissertation on the physics of immature egg cell growth and selection, it was time to pack his bags for his next career move; and to head west…

“I was looking for independent fellow positions, which means you have a small budget, you can choose what you work on, and you have advisors rather than supervisors,” he says. “These are very rare in Europe, but Paris has a large community that works on similar things to me, and I heard about the opportunity at ENS with QBio.”

Quantitative science: A new approach to biology

As a field of study, quantitative biology takes a multidisciplinary approach to the natural world, combining an unlikely cocktail of cell biology, physics, computation, and mathematics. Historically, the various fields of biology, such as zoology, botany and anatomy, have been based on observation and description. “But the problem is that you reach a point where words fail you, and without words, there are observations that you cannot explain to others,” explains Arghyadip. “And that’s where the quantitative aspect becomes truly helpful. For example, in describing how much a tree will grow in proportion to the amount of sunlight it receives. We know the two are related. But how they are related is a matter of experimentation and quantification, and you need a graph to show how that relationship works. So, in essence, we want to describe certain qualities, through quantification, that are not obvious to the human eye.”

Arghyadip’s research focuses on the way that living cells, tissue or entire organisms grow and take shape, a process known as morphogenesis. His preferred tool for doing so is to use the principles of ‘active matter physics’, which describe the way anything from a group of cells to a flock of birds consume energy and produce motion. In some cases this morphogenic process of forming and deforming is dramatic, such as the moment when an embryo transforms from a spherical ball of cells into a multi-layered organism, a process called gastrulation. Scientists believe this is partly down to genetic coding and partly due to the mechanics of cellular interactions – but what is the actual balance between the two and how does nature nearly always get it right, producing seemingly endless healthy embryos ?

"What made me come to ENS was seeing penguin skin for the first time, because it looks like a perfect square lattice, which is good for insulation and living in a very cold climate. "

The heavyweight mystery of feathers

His specific project at QBio seeks to understand how feathers form in various species of birds. “Feathers are analogous to our hair. But our hair does not come out in an ordered way. Whereas, if you look at the skin of a chicken or turkey, the skin is very ordered, with clear patterns. What made me come to ENS was seeing penguin skin for the first time, because it looks like a perfect square lattice, which is good for insulation and living in a very cold climate. But it begs a question: ‘How does it get to be like that? Is it signaling that’s being secreted by the cells? Or are there mechanical properties involved, in the same way that you can sometimes get square waves on a beach? And that’s what I’m working on.”

In practice, that work starts by creating a simple theoretical model using based on experimental data and observations – to build the basic concepts – which is then developed by a combination of theorizing and experimental analysis, culminating in a set of qualitative predictions. Arghyadip then talks to his collaborators, and a set of experiments with skin samples are designed and performed to test the original predictions made by the model.

Paris: An ideal home for scientific research

Not surprisingly, he highlights the fact that “having a multidisciplinary approach is essential. Without it, we couldn’t do what we’re doing today. I’m a trained theoretical physicist, but I’m dreaming up ideas about how to think about feathers in different species of animals: it already sounds far-fetched. But if you want to understand complex natural phenomena, you really need different perspectives, because you might get stuck at points where you need a fresh perspective to move on and solve a problem.”

Fortunately for him, there is no shortage of perspectives within the Parisian scientific community. For a start, since QBio is a hub for theoretical science and has no experimental laboratories, his experiments are carried out by external institutions, such as the Collège de France and the Institut Curie, all of which are in close proximity. “Being in the heart of Paris, geography is not a problem,” he says with a smile. “And what gives you a big advantage by being in Paris is the really high number of very good researchers here. It’s true too for cities like Boston and London, but there are only so many places like this in the world.”

Parisian trains, keeping academics grounded

Another feelgood factor is a Parisian academic community that is very approachable, and a center for digital health research such as PariSanté Campus, which brings together national research bodies and start-up companies. “What I really like about the academic culture here is that everyone is relaxed and humble. Because even if you meet the most famous people in your field, at the end of the day, they all have to take the RER trains to go home… I’m very happy here.”

Having started a three-year chair in March 2022, his immediate aim is to achieve scientific progress in our understanding of the way structures develop in an embryo. “It’s a sculpture that shapes itself, and it gets it right every time,” he says. “There are lots of inner workings to work out, and I want to do that as a physicist. You need inspiration and original ideas, and that’s the long-term goal: to understand the evolution of the natural world.”