Biology subjects

Srikanth, N.

Publications and source records attributed to Srikanth, N..

4 recordsLinked to original sources

bioRxiv2025

Multi Omics Driven Polypharmacology for Osteoarthritis Joint Regeneration

Osteoarthritis (OA) is a common degenerative condition of major joints with no effective cure. Yograj Guggulu (YG) is a well-established polyherbal formulation in Indian traditional medicine for the management of joint disorders. However, its mode of action remains unclear. We integrated multi omics network analysis with a rat model to investigate the effects of oral administration of YG on osteoarthritic joints. YG administration significantly alleviated pain and improved joint function. Imaging and histological analyses reveal that YG protects against structural degeneration in the joint with OA. Proteomic and metabolomic profiling, along with network analysis, uncovered that multiple components of YG alter protein expression in key pathways related to inflammation and cartilage degradation, thus validating the observed clinical effects. The efficacy of YG seems to be the result of the synergistic action of its diverse constituents. Our findings support the use of YG as a multitarget therapy for OA and encourage efforts for the potential repurposing of its active components.

systems biology↗

bioRxiv2023

IRAK4 autophosphorylation controls inflammatory signaling by activating IRAK oligomerization

The controlled oligomerization of signaling proteins is an essential feature of many inflammatory signaling pathways. An example is IL-1 receptor signaling, which relies on the oligomerization of the Death Domain (DD)-containing proteins MyD88 and IRAK family kinases. This process leads to the assembly of the Myddosome signaling complex, and disrupting assembly holds potential for anti-inflammatory treatments. However, IRAKs signaling activity is also regulated by auto-/trans-phosphorylation, and it is unclear if these processes operate at or downstream of Myddosome assembly. Here, we find that the initial stage of Myddosome assembly is solely controlled by MyD88:IRAK4 DD interactions. In later stages, IRAK4 auto-phosphorylation serves as a switch, regulating IRAK1/2/3 incorporation and DD oligomerization. Small molecule inhibitors of IRAK4 kinase activity block this later stage of assembly, explaining how they dampen inflammatory signaling. Our data reveals IRAK4 auto-phosphorylation as an energy-dependent switch activating the heterotypic assembly of IRAKs DDs and downstream inflammatory IL-1 signaling. This highlights how a signaling cascade integrates phosphorylation and protein oligomerization steps.

immunology↗

bioRxiv2023

An optogenetic method for the controlled release of single molecules

We developed a system for optogenetic release of single molecules in live cells. We confined soluble and transmembrane proteins to the Golgi apparatus via a photocleavable protein and released them by short pulses of light. Our method allows for the controlled delivery of functional proteins to cytosol and plasma membrane in amounts compatible with single molecule imaging, greatly simplifying access to single molecule microscopy of any protein in live cells. Furthermore, we could reconstitute cellular functions such as ion conductance by delivering BK and VRAC ion channels to the plasma membrane. Finally, we could induce NF-kB signaling in T-Lymphoblasts stimulated by IL-1 by controlled release of a signaling protein that had been knocked-out in the same cells. We observed light induced formation of functional inflammatory signaling complexes that could trigger IKK phosphorylation in single cells. We thus developed an optogenetic method for the reconstitution and investigation of cellular function at the single molecule level.

biophysics↗

bioRxiv2021

Effect of prophylactic use of intra-nasal oil formulations in the hamster model of Covid-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in upper respiratory tract leading to coronavirus disease 2019 (Covid-19). Severe Covid-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting entry of the virus or its internalization in the upper respiratory tract, are of interest. Herein, we report the prophylactic application of two intra-nasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and Til tailya in SARS-CoV2 infection hamster model. Prophylactic nasal instillation of these oil formulations exhibited reduced viral load in lungs, and resulted in reduced body weight loss and pneumonitis. In line with reduced viral load, histopathlogical analysis revealed a reduction in lung pathology in Anu oil group as compared to the control infected group. However, Til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokines genes, including Th1 and Th17 cytokines for both the intra-nasal formulations as a result of decreased viral load. Together, the prophylactic intra-nasal application of Annu oil seems to be useful in limiting both the viral load and disease severity disease in SARS-CoV2 infection in hamster model.

microbiology↗