Diffraction limited image: Dendrite of a primary hippocampal neuron from SD rat, labelled for GluA1 subunit of AMPAR - DIV21

At the Indian Institute of Science (IISc), our Nanoorganization group has been dedicated to understanding the fundamental processes that govern brain function, with a particular focus on the molecular organization and regulation of excitatory synapses. Our goal is to unravel how key synaptic molecules contribute to the formation, function, and plasticity of synapses, shedding light on brain development and disorders that span from infancy to adulthood, including conditions such as Alzheimer’s Disease. By combining insights from multiple scientific disciplines, we aim to create detailed, data-driven models that capture the dynamics of synaptic biology across a wide range of spatial and temporal scales—from the nanometer level to larger networks, and from millisecond-fast interactions to changes that occur over hours or even longer. These efforts are designed to deepen our understanding of how the brain functions in health and how it becomes disrupted in disease.

A significant focus of our work involves developing advanced imaging tools to study synapses in unprecedented detail. By integrating ultra-high and super-resolution microscopy with techniques like electrophysiology and optogenetics, we strive to capture dynamic changes in the molecular organization of synapses at resolutions as fine as a few tens of nanometers, with millisecond precision. This capability allows us to directly link molecular changes to functional outcomes, offering powerful insights into how synapses operate and adapt. To complement these technological advances, we have been working on using transgenic mouse models and CRISPR-Cas9-based methods for precise labeling of proteins within single cells. These approaches are particularly valuable for understanding how synapses form and change during early brain development and how these processes might go awry in neurological disorders, especially in children.

Our research leverages a diverse range of experimental systems, including rodent models, human-induced pluripotent stem cell (iPSC)-derived neurons, and other model systems, to explore these critical questions. Despite working with limited resources at IISc, the Nanoorganization group has consistently delivered research on par with institutions equipped with larger support systems. This experience has taught us to innovate and make the most of available resources, and we are eager to take these efforts to the next level by developing new technologies and translating our findings to improve human health.

Looking ahead, we aspire to establish a research program that bridges the fields of nanobiology and single-cell biophysics, focusing on how synapses process information and how this knowledge can be used to develop targeted, precision-based therapies. Our vision is to create predictive models that can guide interventions for neurological diseases, ultimately improving health outcomes. With a strong foundation built at IISc and a passion for interdisciplinary collaboration, we are excited about the opportunity to contribute to a deeper understanding of brain function and the development of strategies to combat neurological and developmental disorders. We approach this mission with humility and a commitment to making a meaningful impact through science.