Swati and Akash Bhattacharya’s parents, an English teacher and geologist, did their best to introduce the children to the fun of science when they were young, helping them to engage with the natural world and introducing them to concepts far beyond their level in school, “like fractions in kindergarten,” says Swati. “I’m not sure how much of it actually penetrated, but we always knew that [father] was some sort of scientist and that was a marvelous thing to be.” By the time he was in sixth grade, Akash had put together a home chemistry lab. “Quite soon I was well on my way to making organic indicators and trying to electroplate the household crockery,” he says.
For her part, Swati was attracted to mathematics from an early age, and once her physics lessons began incorporating more math, her interests shifted toward the subject. She was accepted into the physics department of Presidency College, Calcutta, which was a dream come true. Akash found himself following in his sister’s footsteps, and a year after she began her undergraduate studies, he joined her in the physics department at Presidency. “Presidency was awesome,” he shares. “The professors were great, but they did suffer from a regrettable tendency to wonder aloud if I was as capable as my sister. I was not.”
During her undergraduate studies, Swati took several courses under Jayanta Bhattacharjee, which nudged her toward statistical physics. She moved to T. A. Vilgis’ group at the Max Planck Institute for Polymer Research in Mainz, Germany, for her PhD. “The exposure that I got in Mainz was what propelled me to take up biophysics,” she shares. “I worked on polymer physics for my PhD, and my work was primarily computational, but most of the group was actively engaged in biophysics and I was fascinated.”
The siblings’ paths diverged following their undergraduate years. When Akash was considering his path for graduate studies, “My sister pointed out that I did have an aptitude for lab work and I should play to my strengths,” he says. “So that was what I did.” He started his PhD in the NMR spectroscopy lab of Anil Kumar at the Indian Institute of Science (IISc). “This was pure methodology work, long on spin physics, short on pipetting,” he explains. Following the advice of several bio-NMR scientists, including Siddharth Sharma, also at IISc, he moved to the University of Michigan for his PhD work, joining Erik Zuiderweg’s lab in the biophysics department. “Michigan was NMR heaven, with Zuiderweg as senior spin prophet, Al-Hashimi as the up and coming RNA specialist, and Ramamoorthy as the solid-state NMR expert,” Akash says. “This is where I became a card-carrying experimental biophysicist.”
For her postdoc, Swati moved to University of Illinois, Urbana-Champaign, where she worked on computational studies of nanopore sensors in the lab of Aleksei Aksimentiev. “That was when I was properly initiated into the world of biophysics,” she says. “We worked using molecular simulations on various aspects of bionanotechnology, particularly probing nanopore platforms for DNA sequencing. It was exhilarating to work on such ambitious projects while also using the biggest supercomputers in the world.” Following her postdoc, she started as an assistant professor at the Indian Institute of Technology, Guwahati, where her resources were diminished. “I had very few resources initially, and had to start from scratch. That provided me an opportunity to get into a whole new area of method development in computational biology,” she explains. “Faced with a seemingly unsurmountable problem, namely, how to access long timescale dynamics of biomolecules without access to massive supercomputers, I was forced to think deeper. While I had never worked with any method development group before, I became deeply interested in the field and started a whole new line of research. Eventually, as we got more resources, we were able to take up more complex problems.”
During his postdoc at the University of Texas Health Science Center at San Antonio, Akash picked up an important technique, with the help of two mentors. “I started using analytical ultracentrifugation (AUC) because of Professor [Borries] Demeler, who mentored me in this technique. AUC is a first principles hydrodynamic technique that has been around for 90 years, but has finally become easily accessible due to modern supercomputing facilities. AUC has a huge dynamic range and is capable of characterizing the dimeric state of small proteins like insulin all the way to ginormous entities like intact viruses,” he says. “Professor Demeler is a world leader in this technique and it was honestly a bit of a coincidence that we happened to work on the same campus and that my actual postdoc mentor, Professor Dmitri Ivanov, supported me in both learning a new technique and then in burning up lots of resources—such as samples and my own time—in optimizing experiments so that we could study HIV biophysics using AUC. Actually, it is not coincidence, it is good fortune to have such supportive mentors.”
During Swati’s postdoc years, the siblings had once again been on the same continent. “Practically the same neighborhood—the Midwest,” says Swati. “So naturally, we visited each other several times in that period and discussions would often turn to work. We did not actually plan to work together at that time. But later, when I became a faculty [member], it seemed the most obvious thing to do.”
Their decision to collaborate did indeed seem like a natural choice, as their interests lined up and they had developed complementary skills. “Swati is skilled and experienced in MD techniques. I have always wanted to do some MD work on the various HIV related systems that I have worked on, but never had the time to train myself in it,” Akash explains. “Besides, it is not like just using a plate reader, learning MD takes an entire PhD worth of hard work. So, we decided to start working together.”
Akash is a Senior Applications Engineer at Beckman Coulter Life Sciences, where he works on extending AUC methodology to better characterize aggregate formation in biologics, viral capsid genome load, liposome and exosome drug and other cargo loading, and nanoparticles. He moonlights with Swati’s Bhattacharya Lab at the Indian Institute of Technology, Bombay. Her lab works on deciphering SAMHD1, an anti-HIV protein (the project Akash contributes to), and studies rare event acceleration techniques applied to biomolecular systems. “The gap between timescales accessible to biomolecular simulations and many relevant biological processes presents a major challenge. We are developing a suite of techniques to combine rare event acceleration strategies, such as using high-temperature simulations or steered molecular dynamics with kinetic network model (Markov State Model or MSM) building techniques to overcome the timescale challenge,” she explains. “We are also working on applying our methods to a variety of problems.”
The two agree on the best part of working with your sibling, and perhaps more importantly, agree that they haven’t faced any particular challenges because of their familial relationship. As Akash puts it, “I can ask exceedingly stupid questions without embarrassment. That is one of the best things about working with your sibling. You are not going to substantively change the opinion that your elder sister holds about you. That was formed and pretty much set in stone in the early ‘90s.”