WHO?: Suhita Nadkarni
WHAT?: Computational Neurobiologist
WHERE?: Indian Institute of Science Education and Research (IISER), Pune
Established in 2006, the sprawling IISER Pune campus is home to a number of specialised research centres with world-class facilities. One among them is the Computational Neurobiology Lab (CNB), headed by Suhita Nadkarni.
Suhita represents the new crop of young Indian interdisciplinary scientists who refuse to suffer through the slow and bureaucratic approach to science that has been the norm in India. Last year she organised the first meeting for Indian neuroscientists named “No Garland Neuroscience”. This meeting she feels is one way India can contribute to the “intense activity” in neuroscience across the world. “It’s the most exciting time for neuroscience. There are all these great initiatives around the world. There’s BlueBrain, Japan has its own initiative, China has its own initiative. We don’t. And I think we really need to get our acts together and consolidate our resources and skills set and add to this excitement. Each of us can contribute to it. We just need to have a cohesive, strong enough critical mass going.”
“We’ve never been closer but we are not there yet,” she said.
Like many scientific journeys, Suhita’s began — in her words — “with a curiosity about the world, nature around and the general principles that govern these systems”. Growing up in IIT Bombay, she became passionate about physics and decided to pursue research in the field. She earned her PhD in 2005 from Ohio State University. Although her PhD was from the physics department, it introduced her to theoretical and computational neuroscience. She was involved in developing computational models of communication between star-shaped cells called astrocytes and neurons.
“Neurons are the electrically charged cells in the brain that fire electric impulses, while astrocytes are electrically silent with no charge and were hence considered as side-kicks,” explained Suhita. Her PhD was a deep dive to understand how the sidekicks affected communication and memory processing in the brain.
Suhita worked in two labs in the US for her postdoctoral research — Terry Sejnowski’s lab at the renowned Salk Institute and Herbert Levine’s lab at University of California at San Diego. Her mission was to expand our understanding of why astrocytes matter. There were no previous modelling studies that looked into this. Her team was among the first to create a framework for accommodating these new and important entrants to the field of neuroscience. “San Diego is globally considered a hotbed for neuroscience research and offers opportunities for interactions with the world’s experts. The excitement there was palpable and contagious,” she said.
“Those were the most intense and scientifically rewarding periods of my research training. I was fortunate to have amazing mentors who asked the most pertinent of questions. The experience encouraged me to choose my own research problem to work on.”
The Value of Being an Insider
Suhita in her office at IISER Pune, 2017
During those years, Suhita attended and presented her research at meetings of the American Physical Society and American Biophysical Society. “I started off tackling my research questions from the lens of a physicist and a modeller, but these meetings made me realise the value of being an insider — being a neurobiologist rather than a physicist trying to understand the brain. It was important to understand the details before making ‘spherical cow’ assumptions and resorting to oversimplifications typically made by physicists,” she recalled.
“I realised I could not find the answer to these questions about the complexity of the brain by sitting on the fence but will have to jump into it to understand the workings of the human brain inside out!” So Suhita finally took the plunge into the intriguing field of neurobiology.
She is nostalgic about afternoons at Salk Lab, when she and her colleagues would gather for tea. This culture is supposed to have been started by Francis Crick (one of the scientists who is credited with the co-discovery of the structure of DNA based on X-ray diffraction images taken by Rosalind Franklin and colleagues). These informal tea breaks were in reality brainstorming sessions in neurobiology, much to the joy of Suhita, who hungrily took all the knowledge in, straight from the experts. Suhita and her husband Dr Collins Assisi, currently a fellow neurobiologist at IISER Pune, were both postdoctoral researchers at Salk Lab. She recollected how the two of them introduced their colleagues to the Indian-favourite Parle-G biscuits during these afternoon tea breaks while discussing the mysteries of the human brain!
Moving back to India
Suhita and Collins were always certain that they would return to India to establish their research careers. In 2011, they decided to attend India BioScience’s Young Investigator Meeting to learn about job opportunities. That year, the meeting was to take place in Bhubaneswar, so the couple needed to find someone to take care of their one-year-old son while they were participating. She says of the memorable five days of the meeting: “We towed our family all the way to Bhubaneshwar. Our parents, brothers, a sister-in-law and their kids arrived and took up accommodation at a cheaper hotel a block away. Needless to say, there was a lot of back-and-forth traffic in our room, and our son Aalam was snuck in for the night. Fun, adventure and in the end, a very useful trip that shaped our career decisions — of course, made possible only due to the support from our families.”
Even back then, IISER Pune was the top preference for the husband-wife duo.
At IISER, before she could set up her own lab, Suhita had to ensure all the data her lab would generate could be handled by a robust computing system. She had to overcome the challenge of establishing a high performance computing cluster (HPC).
“Finding local technical experts who could build and maintain these clusters was a major challenge since both Collins and I had only been end-users of such clusters prior to our move to IISER. Setting up this facility from scratch was a huge learning experience,” she says. In order to fund this high-performance cluster, Suhita, Collins and their colleague MS Madhusudhan pooled together their Wellcome DBT India Alliance funds with assistance from IISER Pune and their efforts paid off. They succeeded in setting up the supercomputer cluster in 2012, which is now accessible to students from all three of their labs.
Image courtesy: Hippocampus Wikimedia commons, Synapse Wikimedia commons
Modelling neurons
To study this communication between neurons, Suhita finds it useful to compare the workings of the human brain under normal versus diseased conditions. One such disease is Alzheimer’s Disease (AD). AD starts with ‘short-term memory loss’ and later leads to loss of ‘retrieving’ old memories and spatial memory. For example, a patient may forget the way back home. Using AD as a disease model, Suhita’s group looks at different aspects within the synapse that may have gone wrong leading to the disease.
The above figure shows the different components that come together in the reconstruction of the synapse model. The model shown in the figure is a computational model of a CA3-CA1 synapse reconstructed from serial electron microscope images. The CA3-CA1 synapse model figure has been adapted from https://www.slideshare.net/AustralianBioinformatics/how-to-build-a-synapse-from-molecules-membranes-suhita-nadkarni
Synaptic plasticity
Behavioural studies have already shown that the hippocampus, an area of the brain associated with learning and memory, plays a role in the development of AD. Within the hippocampus, experiments have identified defective “plasticity” at the synapse to be one of the causes of AD.
Whenever we recall events stored in our memory, a specific group of neurons is activated to recall the memory. However the ability to activate the correct combination of neurons over all other combinations of neurons is dependent on ‘synaptic plasticity’ or the strength of the neural connections.
Studies have shown that plasticity, or the strength of neural connections, is dependent on the chemical pathways involving calcium in the cell. When these signalling pathways turn defective, plasticity suffers, leading to a loss of cognitive functions. Suhita’s lab is investigating the chronology of these events in AD. For this, they use very detailed calculations to model the synapses.
Reconstructing the synapse is hard work, requiring many elements to be brought in together. “Realistic geometries of the neurons are drawn from electron microscopy images, and then other virtual ‘ingredients’ are added to build the model.” These include information, measurements, features and biophysical properties of various components of the process she wants to model. Analysing so many parameters together requires advanced computation and this is where the computing cluster comes into play.
On being a woman in the STEM field
Suhita with her team at CNB lab.
According to Suhita, IISER Pune has five scientist couples working in the same institute. But, she pointed out that not all places were as welcoming. “Collins and I were told categorically in a few places in personal conversation that they have an internal policy not to hire couples. This is not in accordance with the ethical guidelines set by the Indian Academy of Sciences.”
She counts herself lucky to never have felt discriminated against on the basis of her gender or race. “But it’s foolish to think that this privilege extends to everyone,” she conceded. “One encounters minor incidents of sexism on a day-to-day basis, whether it is while driving or dealing with a technical vendor who continues to ask for the boss despite you informing him that you have the final authority.” How does she handle these situations? “My initial instinct was to pick your battles and make sure that you don’t get saddled with small ones. However, I am now of the opinion that it might be best to deal with any sexism head-on instantly instead of a built-up reaction.”
Organising a one-of-its-kind meeting
Suhita adressing delegates at NGN meeting Image via Suhita
The No Garland Neuroscience — NGN meeting — was borne out of the realisation that India needed a collective that addresses questions in neuroscience that have not been addressed by larger collaborative research groups. “We had a very interesting meeting. I can’t tell you how excited I am about it.”
Suhita and Collins volunteered to organise the first of its kind NGN meeting at IISER Pune that took place in October 2017. This meeting made scientists with families feel welcome by declaring: “We also have a daycare on campus that will be happy to accommodate visiting neurotoddlers and neuropreteens. Feel free to bring your family along and turn NGN into a ‘workation’.”
Scene from the NGN meetin. Image via Suhita
Thanks to these efforts, India finally has a neuroscience meeting which is sustainable, has great scientific content and will serve as a platform to bring together students and researchers wanting to pursue research in this fascinating field. “We know a lot about the brain at the molecular level, but there is still a lot that remains to be discovered. How do abstract entities from our sensory stimuli come together in a physical form in our brain? How do we use this information flexibly to learn and solve problems? We have never been closer to the answers!”
Teaching is an integral part of Suhita’s job at IISER Pune. She is grateful for the freedom to tweak the general syllabus to generate interest among the students. In her words “when the brightest brains choose to study neuroscience, the field and the lab benefit from it”.
This is one article in a series of 30 profiles on the life of science of Indian women scientists whose research has been funded by Wellcome Trust/DBT India Alliance. 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.
