Currently, at Oxford, we study molecular interactions in the immunological synapse, the nanometer-scale gap between immune cells, to uncover fundamental biophysical mechanisms of immune cell activation and tolerance. 

As the sole modeler in the group, I investigate the dynamics of immune synapse formation and T cell signaling using computational modeling and Total Internal Reflection Fluorescence microscopy imaging of supported lipid bilayer (SLB) experiments, in response to self/non-self- antigens and bi-/tri-specific antibodies designed to treat cancers and autoimmune disorders by our industrial partners (e.g., EvolveImmune, Boehringer-Ingelheim, Regeneron). I am also applying my expertise in molecular dynamics to understand how the flexibility of bispecific antibodies impacts their functional performance at the cell-cell interface (Proc. Natl. Acad. Sci. 2025). In collaboration with the Karolinska Institute (Sweden) and AIIMS (New Delhi), we have acquired autoreactive T cell receptor (TCR) sequences from rheumatoid arthritis patients and encoded them in plasmid vectors. Using microbiology and molecular biology techniques, I have generated RNA to encode these autoreactive TCRs into primary T cells, leading to successful electroporation. We plan to use these cells on SLB platforms to study how autoreactive T cells modify immune synapse formation and T cell signaling.

Additionally, I am developing bio-physical models to understand (a) how CD8+ T cells integrate signals from multiple antigenic encounters to enhance their propensity for immune synapse formation, (b) how ligand engagement to TCRs and PD1 impacts microvilli dynamics and early signaling in T cell-APC interfaces (Jenkins*, Fellermeyer*, Heraghty*, Sharma*, Mitra** et al., under revision in Science Immunology), (c) how mobility and cytoskeleton engagement of ligands and receptors in the immune synapse alter the synaptic pattern and downstream signaling (Leithner, Kvalvaag**, Mitra** et al., bioRxiv 2025), and (d) how morphological changes with distinct dynamic characteristics affect T cell-mediated antigen search strategies. 

I focused on agent-based modeling of antibody responses during my postdoctoral research in Germany. We revealed that limited antigen availability, low-affinity seeder cells, and low numbers and quality of T-follicular helper cells adversely impact permissive selection of diverse GC B cell clones, restricting better neutralizing antibody responses (Front. Immunol. 2023). We also explained efficient clearance of motile dead GC B cell fragments by relatively stationary tingible body macrophages in a high-fragment-density environment, which limits autoimmune activation by self-antigens (Cell 2023). Additionally, we demonstrated how a limited number of T follicular regulatory cells can prevent dissemination of self-reactive antibody-secreting cells by inducing apoptosis in self-reactive B cells during the selection or differentiation process in GC (Front. Immunol. 2023).

In the context of neuroinflammation, we have investigated disruption of amyloid homeostasis in response to sleep disruption (Biophys. J. 2020). We also recently explained axonal tau distribution in neurons and somatic tau build up in tauopathy as distinct non-equilibrium steady states using agent-based stochastic model and driven diffusive processes (in preparation).

During the SARS-CoV-2 crisis, we developed an adaptive data-driven algorithm for pandemic preparedness and a novel SARS-CoV-2-specific model integrated with healthcare usage, which influenced public health policies globally (BMC Med. 2021, Commun. Med. 2021, Commun. Med. 2022, PLoS Comput. Biol. 2023). These efforts secured several fundings (e.g., CoViDec, PANDEMOS, and LOKI) for the team. 

In my doctoral research, I showed that emergent adaptive features such as long-lived memory and non-associative learning can originate in intra-cellular signaling networks from distinct timescales of operation for different signaling components and sequestration effects, even in the absence of explicit feedback or inter-pathway crosstalk. By employing a chemical kinetics model of the intracellular signalling, we showed that upon withdrawing the stimulus, the response of the mitogen-activated protein kinase (MAPK) cascade exhibits reverberations over a long timescale, suggesting the emergence of memory (Sci. Rep. 2018). We also examined activation of this cascade, with a train of pulses (arXiv). The resulting adaptive response shows integrative capability over several successive pulses and depicts aspects of non-associative learning, including habituation, sensitization and alternans. 

Concurrently, I analysed empirical data on populations of different immunological cell types collected from newborns and adults to understand how the immune system is altered in adulthood. The adult immune system exhibits a higher degree of correlation in the proportions of cells of the adaptive immune system, suggesting a strong role played by maturation in the evolution of the system. Our analysis validates several correlations between different cell types that have been alluded to in the literature and also suggests a few previously unreported relationships (Chapter 4, Ph.D. thesis).