Prerna beats the cell drums
Posted On: 06-21-2018
A physicist unlocking the mysteries of cell structures shares her findings and her scientific journey
WHO? Prerna Sharma
WHERE? Indian Institute of Science, Bangalore
By Priyanka Sacheti and Aashima Dogra
Prerna’s lab desk is cluttered with stacks of papers and notes. A Native American doll sits in one corner. A cluttered desk is a sign of genius, some say. To this comment, Prerna responds only with a smile.
As she recounted her journey in research at the intersection of physics and biology, it became certain that her modest smile belies her achievements.
“I was a very academic-minded child, always interested in reading books,” she began. “In fact, I used to fight with my mom whenever I returned home from school – she wanted me to take a nap, while I wanted to finish my homework first!”
Years later, not only is Prerna taking forward a niche area of academics, she is also challenging popular notions of being a physics nerd in India. Physics is a gendered space, she agreed, while offering a refreshing outlook from the male-dominated realm of Indian physics.
“Biophysics is the use of physics tools to study biological systems. For example, a large effort in biophysics has been to determine protein structure using x-ray diffraction. This is the same technique that Rosalind Franklin used in 1952 to determine the molecular structure of DNA,” Prerna said.
Keeping up with cell membranes
We know a lot about the cells in our bodies, but some parts of the cell like the cell membrane – the skin of the cell – still remain a mystery. The cell membrane protects the interior of the cell by allowing certain substances into the cell while keeping others out. To do this, its structure must remain stable. This is what a large part of Prerna’s research investigations have been focussed on.
Physically, the cell membrane is a colloidal system – it could be thought of as a liquid made up of many different types of liquid droplets suspended in it. “Curiously, colloidal particles or droplets can spontaneously organise themselves into well-defined structures through a process known as self-assembly,” Prerna explained, setting up the context of her work on cell membranes.
Prerna’s research is inspired by this borderland, but she does not work with cell membranes directly. “The cell membrane actively regulates the transport of ions and materials across the cell. However, like most biological systems, it is very complex, heterogeneous and made of hundreds of different types of lipids and proteins,” she said. Its nanometer-thickness does not make it an easy physical system to study. So, Prerna employs a reductionist approach. Her research uses synthetic colloidal membranes – a far simpler biomimetic model that is a 1,000 times thicker than cell membranes and made up of only one or two components.
“The colloidal membrane is a platform for membrane biophysics. This highly simplified system allows us to probe aspects of membrane mechanics and phase (liquid, solid or gas) behaviour in great depth and figure out generic physical mechanisms that may be relevant to cell membranes.”
Prerna prepares the colloidal membranes by mixing polymers with rod-shaped viruses. The result is a single layer of aligned rod-like particles, that have physical properties similar to that of cell membranes.
This approach of using colloidal membranes in her experiments has proven very effective. In 2014, a research publication in the international journal Nature reported Prerna’s breakthrough discovery about how the cell membrane might be put together.
The big breakthrough
She discovered how colloidal membranes could be kept structurally stable and active without its constituent droplets merging into a single droplet, contrary to how oil droplets merge or coalesce together to separate themselves from water.
This work was inspired by the problem of formation of lipid rafts – tiny clusters of different kinds of lipids and proteins within cell membranes. “One would intuitively expect that these clusters should all merge into one single cluster due to coalescence.” But in Prerna’s experimental conditions, this did not happen.
“The big question in the field was what kinds of interactions could stabilise lipid rafts against coalescence,” she said. For the first time, a model for how a cell membrane could be naturally put together was found. “Our experiment found one pathway to get a stable, cell membrane-like system.”
“At the beginning of my postdoctoral work, my advisor suggested an experimental set-up, which would enable us dynamically change the surrounding pressure of the colloidal membranes. While such a set-up is usually straightforward to put together, complications arose from the mechanical fragility of the membranes,” she recalled.
Prerna had been trying out other ideas of her own in parallel to this rather complicated experiment in the hope to observe colloidal membranes behave in a way that the laboratory had not previously encountered. She tried several samples before she made the breakthrough. Prerna recounted the moment that took a while to sink in: “After seven months of trials, I stumbled on a sample wherein I observed for the first time finite-sized clusters of shorter rods within the host colloidal membranes made up of longer rods.” This study was amongst the first to show that membrane-mediated interactions between the clusters were good enough to impart them stability against coalescence.
Moving with cilia
Since joining IISc in August 2014, Prerna has been focusing on mechanics and phase behaviour of biopolymers. Her lab works with purified bio-polymers – those found in living systems like viruses and bacteria. One of her ongoing projects is searching for good systems to mime the cell organelles called cilia to investigate their assembly and collective ‘beating’.
Cilia are thin, hair-like, microscopic extensions emerging from cell surfaces; in human beings, for instance, cilia can be found in the lungs, respiratory tract, and middle ear to keep airways clear of mucus and dirt, allowing us to breathe without irritation.
“Despite having a detailed knowledge of the cilia structure, we still don’t understand how they collectively move,” explained Prerna. An individual cilium cannot tell us anything about their collective behaviour, so Prerna is studying how the surrounding fluid influences the ‘beating’ movement of cilia. She uses algae called Chlamydomonas to demonstrate that cilia do not beat in isolation.
Physics is gendered space
Prerna has been “incredibly lucky” to have had supportive parents and mentors. “I neither experienced discrimination nor discouragement for being a girl,” she said. She did, however, become aware of gender parities after joining her PhD lab. “I became aware of a lacuna in my educational journey, which proved to be a big handicap – I did not have the right aptitude for experimental research compared to some of my male classmates,” she reminisced.
Prerna feels that societal conditioning encourages boys to be more explorative while excluding girls from doing so. This is a big blow, particularly in pursuing physics, according to her. “Physics was taught to us in high school and college with a great emphasis on its theoretical framework. Both genders progress well up until advanced studies begin. At later stages, one realises that theory and experiments go hand-in-hand. So, though I wished to pursue experimental research work for my PhD, I wasn’t all that prepared to take it up”.
During her undergraduate years at St Stephens in Delhi, she was one of the 10 girls in a class of 30. By the time, she was in the PhD programme at TIFR Mumbai, the gender ratio had already dropped to 1:9. At IISc, the situation is no better. There are three female professors out of 37 in the department.
“There is a policy failure in the system that lets women down as they inch closer to a professional career in academic research.” The “two-body problem” is one example of this. “Most of the times it is the woman who must sacrifice her career. The options for a married woman are laid out simply: give up her work or sign up to the challenging scenario of pursuing her career while living in a different place than her husband.”
Such a fate was unacceptable to the young Prerna, who became a professor at a young age of 28. By then, finding a suitor for marriage became a daunting task. For a long time, she did not come across any prospective partners who would understand her passion for research and be an intellectual equal. The fact that quite a few of her female colleagues were either single or divorced was not comforting either. Prerna likes to call this “the two-body problem in reverse”.
With “a bit of luck”, Prerna said that her fears have faded away. She is happy to have finally found a supportive husband-to-be.
Mentee becomes the mentor
Prerna began her research life at Department of Condensed Matter Physics and Material Science (DCMPMS) in TIFR, as her advisor Shankar Ghosh’s first student. She describes working there as an intense meaningful experience that laid the foundation for training in experimental physics. Prerna feels she connected well with her advisor because of the relatively shorter age gap of 10 years between them. “He inspired his students to do experiments with their own hands and he taught by example,” she added, recalling his ability to design experiments, set up apparatus, and integrate it all into a overall bigger picture. In her time there, Prerna’s findings about the adhesion of colloidal particles to glass substrates were published in Nature Physics.
Following her six years of PhD, Prerna joined as a post-doctoral fellow at Brandeis University, United States, under Zvonimir Dogic who specialises in biophysics. Under his mentorship, Prerna’s interest in biological structures blossomed.
The interview concluded with a tour of her lab, a hushed, reverential atmosphere occupied by students immersed in research, students who today are fortunate to be mentored by Prerna herself.
This is part of a series of profiles of Indian women scientists whose research has been funded by Wellcome Trust/DBT India Alliance. This article was first published on Firstpost. We are thankful for a grant from India Alliance towards this series that has allowed us to invite voices of fellow science writers on this project.