Dr Mukund Thattai, professor of Biochemistry, Biophysics and Bioinformatics at the National Centre for Biological Sciences (NCBS) of the Tata Institute of Fundamental Research (TIFR), located in Bengaluru, has been awarded the Infosys Prize 2023 in Physical Sciences in recognition of his contributions to the knowledge of the development of complex cells. Dr Thattai has ‘studied a problem lying at the crossroads of cell biology and evolution using powerful tools from physics and computer science,’ according to an official release by Infosys. Citing his research on the evolution and function of the Golgi apparatus, the release adds that Dr Thattai has explored the origins of endomembrane organelles, shedding new light on how they emerged from ancient, primordial cells.
Dr Thattai’s research ‘may have profound implications in one of biology’s central mysteries of how complex cells emerged from primordial ones,’ according to the Infosys release.
How a contemporary cell, with its intricate network of organelles, developed from a primitive, or archaeal, cell lacking any of these components is one of the great mysteries of biology. There is evidence that the symbiosis between bacteria and archaeal cells produced a ‘proto-eukaryote’, which was a precursor to the modern cell but did not have endomembranes or internal membranes. Today, cells are made up of a variety of membrane-bound compartments known as organelles, which cooperate to move cargo into, through, and out of the cell. How did the vast majority of organelle types arise, and how did they organise into the self-organising networks found in living cells?
Through the use of DNA sequence data and molecular biophysics, Dr Thattai’s research is able to physically reconstruct the evolution of new organelles by travelling back in time. He identified that new endomembrane organelles could arise as a result of the evolution of vesicle trafficking proteins. By incorporating concepts from information theory and statistical physics with rich bioinformatics, he has investigated the evolution of organelle networks in cells. Dr Thattai demonstrated how the fundamental vesicle trafficking pathways within the cell inevitably led to the Golgi apparatus’ distinct organisation.
Dr Thattai joined the NCBS, Bengaluru, in 2004, the same year he obtained a PhD from the Massachusetts Institute of TechnologyThe Simons Centre for the Study of Living Machines at NCBS was founded with the assistance ofDr Thattai. It has become one of the major worldwide hubs for work at the nexus of biology and physics under his direction. He also had a key role in the founding of the Simons-NCBS Monsoon School on the Physics of Life and the ICTP-ICTS Winter School on Quantitative Systems Biology, which for more than ten years have drawn hundreds of bright scholars and postdocs to this multidisciplinary field. In each of these approaches, Dr Thattai has contributed to the development of a new generation of computational biologists and elevated India’s profile in a fascinating and quickly expanding subject.
All Images Courtesy: Infosys
Although Dr Thattai has a background in physics, his employment at the NCBSis illustrative of how biology has increasingly become an interdisciplinary field, encompassing everything from advanced experimental techniques to novel data analysis required for intricate biological investigations.
At NCBS, Dr Thattai got the opportunity to “rearticulate the problem for myself”. He chose to concentrate on the membrane-trafficking systems, which control the movement of materials both within and outside of cells, as one specific component of biological mechanisms. He was also able to attend a three-month workshop at the esteemed Kavli Institute for Theoretical Physics in Santa Barbara, California, USA, with the assistance of Prof Satyajit Mayor, then director of NCBS.
Following the workshop and subsequent discussions, Dr Thattai investigated how eukaryotic cells diverged from prokaryotes by comprehending the physics behind membrane trafficking mechanisms. His study was part of an emerging field of physics called bio-physics, as well as new ground requiring a thorough understanding of both biology and physics.
Dr Thattai’s interest in mathematics and physics was piqued at school by the 13-part television series Cosmos: A Personal Voyage, hosted by American astronomer Carl Sagan and telecast on Doordarshan in the 1980s. He even submitted an application to Cornell University, where Sagan had a professorship but unfortunately, did not get a chance to be introduced to the legendary scientist. When Dr Thattai enrolled in college, Sagan’s cancer was already quite advanced, and he died before Dr Thattai could meet him.
Subsequently, Dr Thattai applied to the Massachusetts Institute of Technology’s (MIT) graduate programme, concentrating on condensed matter theory. Condensed matter systems, which are made up of several interacting constituents, such as atoms and electrons, each of which is simple on its own but behaves in complicated and surprising ways when combined, has influenced several areas of study in physics. In this microscopic complexity, emerging simplicity can occasionally be found. Dr Thattai was first exposed to this branch of biology that he had never heard of before in the early 2000s.
After enrolling in a graduate-level course on biomolecular computation taught by neuroscientist and physicist Sebastian Seung, Dr Thattai studied articles discussing the application of electrical circuit mathematics to the combining of genes. Subsequently, he became one of the first three doctoral students of Dutch biophysicist Alexander van Oudenaarden, a pioneer in the fields of single-cell RNA measurements and stochastic gene expression. He started an experimental lab at NCBS in 2004 to further his research interests after joining the school. However, he soon started researching the development of cells. Additionally, Dr Thattai ran a programme named Evolutionary Perspectives on Evocell2010 for three months in 2010 at the University of California, Santa Barbara’s Kavli Institute for Theoretical Physics.
*The writer is Associate Editor, Science India.
