Ms. Shirsha Saha
Ms. Shirsha Saha has been selected for the Sun Pharma Science Foundation Science Scholar Fellowship - 2024 for Young Scientists in the field of Biomedical Sciences. She was awarded for her research entitled, “Molecular mechanism of distinct chemokine engagement and functional divergence of the human Duffy antigen receptor”. This work is focused primarily on the structure and function of the human Duffy antigen receptor for chemokines, an enigmatic seven transmembrane receptor that lacks canonical transducer-coupling and downstream signaling pathways, unlike prototypical GPCRs. This receptor serves as one of the most promiscuous chemokine binding protein in our immune system, and also the primary anchor site for the malarial parasite, Plasmodium vivax, as well as for the pore forming toxins secreted by Staphylococcus aureus. Shirsha combined biochemical, cellular, pharmacological, and structural approaches, to illuminate the intricate details of ligand-recognition, activation, functional divergence, and potential non-canonical signaling pathways downstream of this intriguing receptor, with direct implications for novel drug discovery. This is truly a pathbreaking discovery representing an area that was being pursued by multiple laboratories across the globe, and her findings were recently published in Cell (2024).
Ms. Dipasree Hajra
Ms. Dipasree Hajra has been selected for the Sun Pharma Science Foundation Science Scholar Fellowship - 2024 for Young Scientists in the field of Biomedical Sciences. She was awarded for her research, “Understanding the mechanism of host deacetylases SIRT1 and SIRT3 in the modulation of Salmonella pathogenesis”. Her research focuses on the role of two critical sirtuins, SIRT1 and SIRT3, in influencing host and intracellular Salmonella metabolism by mediating an immune-metabolic switch in their infected host. Her investigation revealed that live Salmonella Typhimurium could actively regulate the levels of SIRT1 and SIRT3 via its virulence SPI-2 effector protein, steE. Salmonella-induced elevated levels of SIRT1 and SIRT3 triggered a polarization of macrophages from a pro-inflammatory M1 state to an immunosuppressive M2 state, creating a conducive environment for its intracellular survival. Upon SIRT1 or SIRT3 knockdown or inhibition, the intracellular Salmonella underwent a metabolic shift toward high fatty acid oxidation and low glycolysis, consequently reducing proliferation within macrophages, while the host resorted to reduced fatty acid oxidation and heightened glycolysis. Interestingly, knockdown or inhibition of these sirtuins in an in vivo mouse model of infection led to higher organ burden and increased dissemination owing to elevated reactive oxygen species, IL-1β, and IL-6 production. Furthermore, her study explored SIRT1 and SIRT3’s role in the maintenance of mitochondrial bioenergetics, dynamics, and host-Salmonella pH balance during Salmonella infection. Her crucial findings indicate that Salmonella strategically modulates the levels of SIRT1 and SIRT3 to maintain its metabolism, contributing to successful intracellular pathogenesis. Altogether, her study intends to understand the complex and multifaceted intricacies of host-Salmonella dynamics aiming to develop host-targeted therapeutics to thwart Salmonella's burden.
Mr. Souradeep Dey
Mr. Souradeep Dey has been selected for the Sun Pharma Science Foundation Science Scholar Fellowship - 2024 for young scientists in the field of Biomedical Sciences. His award-winning research work was entitled, “Microfluidic Human Physiomimetic Liver Model as a Screening Platform Recapitulates Intrinsic and Idiosyncratic Drug Toxicity”. In line with the evolution of in vitro liver models, his research work focussed on bioengineering a microfluidic human physiomimetic liver model using transdisciplinary technologies for assessing diverse phenotypes of drug induced liver injury with more human specific sensitivity. In this pioneering research work, he applied 3D printing and microfluidic technology to bioengineer a human physiomimetic liver acinus model (HPLAM) which recapitulated the radial hepatic cord-like structure with functional sinusoidal microvasculature network, biochemical and biophysical properties of the native liver acinus. Intriguingly, the developed human derived hepatic cells incorporated HPLAM cultured under physiologically relevant microenvironment, acted as metabolic biofactories manifesting enhanced hepatic functionality, secretome levels and biomarkers expression over several weeks. As per his research findings, the matured HPLAM reproduced dose- and time-dependent hepatotoxic response of human clinical relevance to drugs typically recognized for inducing diverse DILI phenotypes. Overall, the developed HPLAM emulated in vivo like liver functions and may provide a useful platform for DILI risk assessment to better determine safety and human risk. Souradeep is currently pursuing his Ph.D. under the supervision of Prof. Biman B. Mandal at the Centre for Nanotechnology, Indian Institute of Technology Guwahati (IITG). His research interest lies in utilising 3D bioprinting, stem cells and microfluidic platforms to develop dynamic 3D in vitro tissue models for disease modelling and drug screening applications.
Ms. Oyahida Khatun
Ms. Oyahida Khatun has been selected for The Sun Pharma Science Foundation Science Scholar Fellowship 2024 for young scientists in the field of Pharmaceutical Sciences. Her award-winning work was titled “Dissecting Molecular Interactions Between SARS-CoV-2 and Human Cellular Factors: Antiviral Targets and Viral Immune Evasion.” Her research focused on host-directed therapeutics development against SARS-CoV-2 and identifying the viral proteins that antagonize the cellular antiviral response. She aimed to identify the host factors constantly upregulated at the upper respiratory tract (URT), the primary site of infection, understand their role in virus pathogenesis and disease progression and explore their potential as host-directed therapeutics. In this endeavors, she has performed meta-analysis using the transcriptome and proteome datasets, where samples were collected from the nasopharyngeal swab and bronchoalveolar lavage fluid (BALF) of COVID-19 infected patients and healthy individuals as control. In doing so, she successfully identified thioredoxin as the most consistently upregulated host factor at the URT. Building on this, she has tested the antiviral activity of Auranofin, an FDA-approved inhibitor of thioredoxin reductase, a key enzyme regulating the activity of thioredoxin. In vitro and in vivo testing demonstrated the efficacy of Auranofin in mitigating SARS-CoV-2 replication in cell culture and pre-clinical hamsters. Furthermore, she has explored the antiviral efficacy of Auranofin in combination with other COVID-19 direct-acting antivirals (DAAs) in vitro to minimize the adverse effects of DAAs while enhancing protective antiviral activity against SARS-CoV-2. In parallel, she has identified ORF6, a small protein of SARS-CoV-2, antagonizes the innate immune pathway, the first line of the host defense mechanism against pathogen infection. She has demonstrated that ORF6 suppresses interferon (IFN) production by targeting critical immune proteins for degradation. Oyahida has finished her PhD recently under the supervision of Dr. Shashank Tripathi at the Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore. Her research interests are twofold: first, to develop host-directed therapeutics against SARS-CoV-2 infection; second, to identify SARS-CoV-2 proteins that antagonize the host innate immune machinery and characterize the viral evasion and antagonism strategies.
Ms. Seema Kuldeep
Ms. Seema Kuldeep has been selected for The Sun Pharma Science Foundation Science Scholar Fellowship 2024 for young scientists in the field of Pharmaceutical Sciences. Her award-winning work was titled “Macrophage GPCR Signaling as a Potential Therapeutic Target for Treating Obesity and Diabetes.” Her study conducted groundbreaking research exploring the role of Gi-coupled G protein-coupled receptor (GPCR) signaling in macrophages and its impact on metabolic diseases such as obesity and Type 2 Diabetes (T2D). She utilized a cutting-edge chemogenetic approach, employing LyzM-GiD mice to selectively activate Gi signaling in macrophages via the designer receptor hM4Di. Through comprehensive metabolic and molecular studies, her research demonstrates that activation of macrophage Gi signaling exacerbates inflammation, glucose metabolism impairments, and lipid homeostasis disruptions, hallmarks of T2D. Overall her study identifies Gi signaling in macrophages as a promising therapeutic target for metabolic disorders, offering potential for innovative treatments that mitigate inflammation and metabolic dysfunction.