This is Part I of Vishwadeep Mane’s (VM) conversation with Professor Utpal Nath (UN) and Prof. Olivier Hamant (OH). The interview revolves around the robustness of organs, shape, and size from a mechanical and genetic perspective. It takes a walk around the historical aspects of plant development and the turning points that led the interviewees to study robustness. The interview also revolves around robustness and its relation to the school of philosophy. And, finally, what can we learn more about robustness from the plants?
VM: Could you briefly describe your background and how you became interested in developmental biology?
UN: Hi. This is Utpal Nath from the Department of Microbiology and Cell Biology at the Indian Institute of Science, Bangalore, India. I did a BSC in agriculture at one of the state agricultural universities in West Bengal. At that time, I had no idea what I wanted to do. Sometimes, I wanted to be a geneticist; other times, a soil scientist, and so on. This kept changing, which was okay. And as a student, it is OK to be undecided or undetermined.
I took genetics as one of my subjects. I liked genetics and the tiny mathematical twist that gives essence to its principle. After my BSc, I wanted to continue my studies but had yet to decide what to do. I took a national eligibility test, got selected, and went to Coimbatore, about 2000 kilometers from my hometown. There, I got into an MSc program in biotechnology. Since I wanted to continue my studies, I did a PhD and got into TIFR-NCBS. I have always liked proteins, their structure, and their function. Attesting to that love, the only book I have probably read cover to cover in my life is The Lehninger. At TIFR-NCBS, I joined Prof Jayant Udgaonkar’s laboratory, working on protein kinetics and folding.
I had a lovely time during my five to six years at NCBS. For the first time, I learned how to do science- ask questions, address them, interpret the data, and draw conclusions. By then, I had completed protein-protein chemistry, biochemistry, and biophysics. Since I had some plant background, I thought it would be nice to go back to plant research and ask some atypical questions that are not necessarily straightforward. I tried many labs, and Prof Enrico Coen (JIC, Norwich, UK) agreed to accommodate me as a postdoc in his lab. That’s when I started working on organ growth and shape and realised it has some nice geometric twists and shapes. That’s when I got interested, and I have continued in the same area ever since.
OH: I’ve always been interested in plant development, even as a kid. As a PhD student working with Véronique Pautot (INRA, Versailles) and Gerrit Beemster (VIB, Ghent, Belgium), I studied the regulation of meristem function by a set of highly conserved transcription factors in Arabidopsis. After this, I moved to a completely different field, meiosis in maize, with the group of Zac Cande at UC Berkeley (USA), where I identified and characterised the first plant- shugoshin, a protein controlling chromosome segregation.
After this, I moved to Lyon (France), where I started my current work on the role of mechanical signals in plant morphogenesis, bridging molecular and cellular biology with modelling and biophysics.
VM: Thank you very much! Were there any pivotal moments or influences in your career that directed you toward this specific study area of plant developmental biology?
UN: I started getting interested in this area from Rico’s (Enrico Coen) lab. His approach was that, in science, no matter what you do, you get a general message from every experiment. That is very important, and all students should learn that. For example, if you see leaf growth, you can always compare it with animal organ growth or even with human-made structures like monuments and see how they connect. That is what I learned at that time.
The pivotal moment came later when we analysed the CINCINNATA mutant. We realised something was wrong with the surface curvature but couldn’t develop a generalised problem. There is more growth in one place than the other, and it changes the flatness of the leaf. It was not me but Rico who came up with the idea that we could explore how genetics affects growth and, subsequently, the surface curvature.
The exciting part of development biology is that you see a structure frozen in time when you look at a plant, a flower, or a leaf. That structure develops over time, and it’s incredible how things change in the time dimension! Since then, I have remained interested in growth and mathematics. Since development follows specific rules, the rules must have a mathematical relevance.
OH: Plant biology has been a fascinating subject to me since my childhood. As I studied biology, I was frustrated by the relatively siloed view of biology. All changed with systems biology and systems thinking with more holistic approaches. Robustness came in that context: when one asks how organ shape reproducibility arises, one must look at interactions and their counterintuitive outcomes. Our Cell paper in 2012 was probably the first step in that direction, showing how mechanical conflicts are actively fueled in development.
VM: How would you define robustness in the context of developmental biology?
UN: I heard about the mechanical influence on growth only a few years ago when I started interacting with my colleagues who work on this, especially the mechanical aspect of plant growth. Mostly, it was a contribution from Olivier as he was working on it. That’s when I started getting familiar with this concept.
When you say robust, you are in a specific position and want to stay in the same position, irrespective of the influences or disturbances from the internal or external environment. Differential growth tries to change you, but you want to stay where you are! So, if this is robustness, I would compare it with the concept of homeostasis we learned in school. What is homeostasis? If I am a system, I want to stay where I am, no matter how many parameters are working on me to try and change that. And once homeostasis is disrupted, returning to that state becomes even more challenging.
OH: Robustness is the ability of a system to maintain its stability despite fluctuations. In developmental biology, those fluctuations are local growth conflicts, shape changes, etc. Thus, it’s the exact definition; only the context is specified (local, not environmental). In ecology, robustness instead refers to responses to environmental fluctuations.
VM: There is a nice parallel between homeostasis and robustness, and it operates from an atomic level to the cosmic scale. What are some key historical milestones in developmental biology related to robustness or homeostasis that you have come across?
UN: I only recall a few of them. However, one thing I was asked to read about was epigenetics. I was surprised to learn that gene function changes without any sequence changes are called epigenetics. For example, in early embryogenesis, the genetic constitution of those few thousand cells is identical, but they have very different fates due to subtle epigenetic traits. I thought that was a milestone.
Throughout the 90s, many labs were working on flower development. Elliott Meyerowitz gave a talk at the faculty club at IISc, which I attended as a PhD student. He explained the ABC flower development model, showing mutants classified into three categories” A, B, and C. He described how several genes come together to create a perfect flower, even though they don’t “know” how to do it. This process happens for millions of flowers with similar outcomes, which I found fascinating.
I was very impressed by the talk and returned to NCBS, which was on the IISc Campus then. Rico gave a talk that was essentially the same in a different model system, Antirrhinum Majus. Despite 75 million years of difference between Arabidopsis and Antirhinnum, they follow similar principles and produce the same outcome with some variation. This was mind-boggling for me.
Another turning point came with the CINCINNATA mutant. We studied leaves that mature from the tip to the base, appearing as a wave traversing from tip to base. The base continues to grow up to a certain distance, and as growth occurs, the leaf matures and moves upward. So something is moving from top to bottom. I began to think about how leaf size and shape diversity in nature depend on the speed of this movement. After joining as an independent PI, I decided to study this. To test this, we marked nail paint at different leaf positions and tracked growth at various development stages in many species. We realised that other sizes, shapes, and species have different growth patterns. This eventually led me to study the genetic basis of shape and size with a little bit of mathematics over the past 2 decades.OH: I have been influenced by multiple personalities, which has driven me to study robustness in plant systems. The works and people include, but are not limited to, Jean-Pierre Aubin’s theory of viability, Dennis Meadows and Robert Ulanowicz’s theory of the balance between efficiency and resilience, and many system analysts. Analogies with soap bubbles and other soft matter are at the origin of plant biomechanics (see D’Arcy Thompson). Many of these theories are wrong, but they were essential to put us on the right track and merge biology and physics (as it was in antiquity).
Stay tuned for part 2!
