Aadesh Kapadne

The i3C BRIC RCB is a flagship PhD initiative of the Department of Biotechnology (Govt. of India), established to train scientists to address urgent national and global challenges. Ranking 38 out of ~8,000 JRF awardees through rigorous interviews, I secured my first-choice research project on developing monoclonal antibody therapy against Chandipura virus-a high mortality outbreak pathogen endemic to central and southern India. While initial symptoms like fever, vomiting appear mild, cases rapidly escalate to meningitis and acute encephalitis, ending in coma and death within 24–48 hours of neurological symptom onset. With case fatality rates of 35–79%, marked pediatric vulnerability, particularly in children <15 years, and no standardized diagnostics or treatment available, the clinical timeline precludes vaccine-induced immunity (~7–14 days). This therapeutic gap demands immediate viral neutralization upon administration—the focus of my doctoral research.

My role centers on characterizing humoral B-cell responses to Chandipura virus infection, identifying protective antibody isotypes, temporal dynamics of antibody-producing cells, and epitope specificity to guide therapeutic candidate selection. Our methodology isolates PBMCs from recovered and acutely febrile patients, sorts single cells, clones antibody-producing genes into mammalian cell lines, and screens for neutralization capacity.

I am part of a multi-institutional collaboration spanning the Immunobiology Laboratory (NCCS, Pune), National Institute of Immunology (NII, New Delhi), and ICGEB-Emory Joint Vaccine Center (ICGEB, New Delhi), with active engagement across all three institutes throughout my doctoral tenure.

Recently, our team has begun integrating computational structural biology tools like AlphaFold, Rosetta, RFdiffusion into our antibody discovery pipeline. This work has equipped me to distinguish when AI-driven predictions align with experimental evidence versus when they require validation.

During my dissertation, I investigated how repeated mild traumatic brain injury (rMTBI) affects cognitive functions, memory, and induces PTSD-like symptoms in rats. Previous research demonstrated that rMTBI, induced using a weight-drop injury paradigm, results in cognitive deficits, impaired memory, reduced expression of memory-related genes (e.g., BDNF, NR2B), and increased HDAC binding at their promoters.

Notably, interventions like Fecal Microbiota Transplant or supplements of Lactobacillus rhamnosus GG (LGG) and short-chain fatty acid (SCFA) —sodium butyrate in trauma-exposed rats significantly improved cognitive deficits and normalized disrupted gene expression levels caused by rMTBI. These interventions were also associated by increased binding of HATs on gene promoter regions.

In my study, I hypothesized that gut-microbiota interventions could influence hippocampal synaptic plasticity gene expression through SCFA metabolites and their receptor activation. My focus was on butyrate, activating G-Protein coupled receptors like FFAR2 or acting as an epigenetic regulator (HDAC inhibitor), potentially leading to downstream NFkB activation and chromatin remodelling.

To investigate this, I isolated RNA and total protein from the hippocampus of trauma-exposed rats supplemented with LGG. Utilizing qRT-PCR and Western blot analysis, I assessed gene and protein expression levels of the SCFA receptor—FFAR2. Additionally, I developed an incremental protocol enhancing nuclear protein yield by 35%, critical for studying the nuclear translocation of NFkB—a key factor in epigenetic regulation. The subsequent Western blot analysis of cytosolic and nuclear protein fractions fortified our theory that NFkB translocates from the cytosol to the nucleus, instigating epigenetic changes and altering the expression levels of synaptic plasticity genes.

During my bachelor's research, I delved into the world of endophytic microorganisms, known for their capacity to synthesize diverse and potent chemical compounds. This led me to focus on Eucalyptus spp., a medicinal plant celebrated for its potent pharmacological properties in Indian Ayurveda. Despite its significance, the endophytic microbiota of the Eucalyptus spp. remained largely unexplored. Understanding the endophytic microorganisms within this plant could potentially unlock antimicrobial and antioxidant agents of great value.

To initiate this exploration, I optimized a surface sterilization protocol for a variety of eucalyptus plant tissues. This fine-tuning resulted in a 43% increase in the successful isolation of bacterial and fungal endophytes. Moving forward, I conducted a thorough examination of endophytic fungi distribution across different parts of the eucalyptus plant. Remarkably, leaves emerged as the primary hub for these endophytic organisms, followed by twigs and stems in descending order of isolation rates.

In furthering the study, I successfully isolated 16 species of endophytic fungi displaying remarkable antioxidant potential, with over 65% efficacy demonstrated through multiple assays, including DPPH free-radical scavenging, total phenolic content estimation, and ferric-reducing antioxidant power assessments. These findings strongly suggest the ability of these endophytes to produce bioactive metabolites with significant biological benefits.