This year’s Breakthrough Prizes, sometimes dubbed the ‘Oscars of science’, were announced on September 22. With a reward of USD 3 million each, these are currently the most lucrative science prize in the world, topping even the Nobel Prizes! This time, eleven researchers were recognised for their discoveries in fundamental physics, life sciences and mathematics.
Clifford P Brangwynne and Anthony A Hyman shared a prize for discovering a new mechanism of cellular organisation. Until this discovery, the dominant presumption was that most cellular activities take place in membrane-bound cellular subunits called organelles. However, Brangwynne and Hyman’s research revealed the widespread presence of liquid-like droplets or ‘phase separations’ which act as temporary mini-reactors where many important biomolecular reactions routinely take place.
Having worked with Clifford Brangwynne during her postdoctoral research, Sravanti Uppaluri is no stranger to the immense potential of the discovery of these droplets. The biologist and faculty member at Azim Premji University explained, “Just like oil and water, when proteins and RNA molecules come together, they form a separate phase which can serve as another compartment where reactions take place. These phase separations can be a lot more dynamic as they can quickly disassemble and assemble as needed.”
“Just like oil and water, when proteins and RNA molecules come together, they form a separate phase which can serve as another compartment where reactions take place. These phase separations can be a lot more dynamic as they can quickly disassemble and assemble as needed.”
Sravanti added that the discovery of these phase transitions has brought on a new paradigm of thinking about how cells organise themselves. This is clear from the number of studies that have since revealed these cellular droplets’ role in crucial processes like gene regulation as well as in debilitating diseases like Alzheimer’s disease. They have also been shown to have a role in deactivating viruses, even the COVID-19 virus.
The Hyman-Brangwynne discovery stands out from most other biological phenomena because of the way it has captured the imaginations of physicists just as much as that of biologists.
“We are used to thinking of cells as something that belongs to the domain of biology. But anyone can look at the cell and recognise how wonderful it is and try to explain what is going on inside it,” said Kripa Gowrishankar, physicist and faculty member at the university.
Kripa, who studied phase separations on the cell membrane during her PhD, pointed out that phase transitions and phase separations have been a traditional topic of study in physics for a long time, typically in the context of intermolecular interactions in mixtures, for example of water and oil. “Physicists are used to doing these kinds of experiments in a controlled lab environment. It’s very different when this happens inside a cell. It’s an amazing thing for anyone to study.”
“Physicists are used to doing these kinds of experiments in a controlled lab environment. It’s very different when this happens inside a cell. It’s an amazing thing for anyone to study.”
Both Sravanti and Kripa imagine a future where understanding these mechanisms inside the cell could inspire applications outside the cell too, such as in the field of synthetic biology. “You could create some sort of catalytic mechanisms or centres for the production of some chemicals that are needed,” mused Kripa.
“The possibilities seem endless,” said Sravanti. “The fact that there has been so much work just in the last 10 – 12 years is a reflection of the fact that so many disciplines are coming together. So many new experimental techniques have come up to probe and manipulate this phenomenon inside and outside the cell — this has been exciting!”
Kripa added, “Using all practical considerations, a cell shouldn’t be working at all! The fact that life works and we are living… can’t be magic, right? There has to be some physics behind it. The fact that it is doing this stuff at such a small scale, regulating the formation and disintegration of organelles… it’s quite lovely.”