Biology subjects

Joshi, S. V.

Publications and source records attributed to Joshi, S. V..

5 recordsLinked to original sources

bioRxiv2024

Peptide Mold: A Novel Strategy for Mapping Potential Binding Sites in Protein Targets

A novel concept titled Peptide Mold for mapping potential binding sites in protein targets is presented. A large multiconformer tetrapeptide library comprising of 32 million conformations of all possible combinations of naturally-occurring amino acids was constructed and used for molecular docking analysis in the substrate-binding site of SARS-CoV-2 PLpro enzyme. The top-ranking, structurally-diverse tetrapeptide docked conformations (symbolizing peptide mold, analogous to a clay mold) were used then for elucidating a five-point pharmacophore. Ligand-based virtual screening of a large, multiconformer library of phytoconstituents using the derived five-point pharmacophore led to identification of potential binders for SARS-CoV-2 PLpro at its substrate-binding site. The approach is based on generating the imprint of a macromolecular binding site (cavity) using tetrapeptides (clay), thereby generating a reverse mold (with definitive shape and size), which can further be used for identifying small-molecule ligands matching the captured features of the target binding site. The approach is based on the fact that the individual amino acids in the tetrapeptide represent all possible drug-receptor interaction features (electrostatic, H-bonding, van der Waals, dispersion and hydrophobic among others). The peptide mold approach can be extended to any protein target for mapping the binding site(s), and further use of the generated pharmacophore model for virtual screening of potential binders. The peptide mold approach is a robust, hybrid computational screening strategy, overcoming the present limitations of structure-based methods, e.g., molecular docking and the ligand-based methods such as pharmacophore search. Exploration of the peptide mold strategy is expected to yield high-quality, reliable and interesting virtual hits in the computational screening campaigns during the hit and lead identification stages.

bioinformatics↗

bioRxiv2024

The ChAHP chromatin remodelling complex regulates neurodevelopmental disorder risk genes to scale the production of neocortical layers

Although chromatin remodellers are among the most important risk genes associated with neurodevelopmental disorders (NDDs), the roles of these complexes during brain development are in many cases unclear. Here, we focused on the recently discovered ChAHP chromatin remodelling complex. The zinc finger and homeodomain transcription factor ADNP is a core subunit of this complex, and de novo ADNP mutations lead to intellectual disability and autism spectrum disorder. However, germline Adnp knockout mice were previously shown to exhibit early embryonic lethality, obscuring subsequent roles for the ChAHP complex in neurogenesis. Here, we employed single cell transcriptomics, cut&run-seq, and histological approaches to characterize mice conditionally ablated for the ChAHP subunits Adnp and Chd4. We show that during neocortical development, Adnp and Chd4 orchestrate the production of late-born, upper-layer neurons through a two-step process. First, Adnp is required to sustain progenitor proliferation specifically during the developmental window for upper-layer cortical neurogenesis. Accordingly, we found that Adnp recruits Chd4 to genes associated with progenitor proliferation. Second, in postmitotic differentiated neurons, we define a network of risk genes linked to NDDs that are regulated by Adnp and Chd4. Taken together, these data demonstrate that ChAHP is critical for driving the expansion upper-layer cortical neurons, and for regulating neuronal gene expression programs, suggesting that these processes may potentially contribute to NDD etiology. HighlightsO_LIAdnp and Chd4 cKOs exhibit similar deficits in cortical growth C_LIO_LIAdnp sustains the proliferation of apical progenitors to scale the production of upper-layer neurons C_LIO_LIAdnp recruits Chd4 to genes involved in corticogenesis C_LIO_LIAdnp is a master regulator of risk genes associated with neurodevelopmental disorders C_LI

neuroscience↗

bioRxiv2022

Comparative whole plastome and low copy number phylogenetics of the core Saccharinae and Sorghinae.

AO_SCPLOWBSTRACTC_SCPLOWDespite over 60 years worth of taxonomic efforts, the relationships between sugarcane (Saccharum hybrid cultivars), Sorghum and their closest evolutionary relatives remain largely unresolved. Even relationships between generally accepted genera such as Miscanthus and Saccharum have not been examined in any large-scale molecular detail. Genera such as Erianthus, Miscanthidium and Narenga pose even greater taxonomic contention. Erianthus is not monophyletic and Erianthus sect. Ripidium (Valdes and Scholz 2006, Lloyd Evans et al. 2019a; Welker et al. 2019) represents a distinct and separate genus, Tripidium Scholz. Miscanthidium is placed within Miscanthus by many workers, whilst the New World Erianthus species and Narenga are currently placed within Saccharum. As these species represent a significant portion of the gene pool that sugarcane breeders use for introgression into sugarcane, their taxonomic placement and relationships to Saccharum are of significant economic import. Erianthus species from the Americas have not been significantly employed in sugarcane breeding and may represent an untapped genetic resource. In an attempt to resolve the taxonomic relationships of these genera, we have assembled three novel chloroplasts, from Miscanthidium capense, Miscanthidium junceum and Narenga porphyrocoma (this latter assembled from transcriptomic and long read data). In parallel, five low copy number loci have been assembled from species within Saccharum, Miscanthus, Sarga and Sorghum. Phylogenetic analyses were performed using both low copy number genes and whole chloroplasts. The phylogenetic results were compared with karyotype data to circumscribe the genera most closely related to sugarcane. We reveal that genera Miscanthus and Saccharum are monophyletic and have never undergone polyploidization outside their own genera. Genera Erianthus, Miscanthidium and Narenga are allopolyploids, which excludes them from being members of Saccharum and Miscanthus. Moreover, all three of these genera have divergent evolutionary histories. We therefore support the use of the genera Miscanthus, Miscanthidium, Erianthus (for the New World Species) and Narenga for those species and genera most closely allied to Saccharum. Our data demonstrate that all these genera should be excluded from Saccharum sensu lato.

evolutionary biology↗

bioRxiv2020

On the Validity of the Saccharum Complex and the Saccharinae Subtribe: A Re-assessment

The Saccharum Complex represents an hypothetical collective of species that were supposedly responsible, through interbreeding, for the origins of sugarcane. Though recent phylogenetic studies have cast doubt on the veracity of this hypothesis, it has cast a long shadow over the taxonomics of the Andropogoneae and the Saccharinae subtribe. Though evidence suggests that Saccharum s.s. is comprised of only three true species, according to Kews GrassBase there are as many as 34 species in Saccharum s.l. Our recent work has shown that many of these species are millions of years divergent from Saccharum. As the Saccharum complex represents the species that sugarcane breeders attempt to introgress into sugarcane, and as the Saccharinae, in its current form, covers almst 12 million years of Andropogoneae evolution an update on the extents of the Taxonomic and customary groupings is much needed. Based on the latest sequence based phylogenies and the inclusion of traditional taxonomics we develop an integrated view of the Saccharinae + Saccharum complex species in the context of the major groupings within the Andropogoneae. We use this phylogeny to re-circumscribe the limits of both the Saccharinae subtribe and the Saccharum complex group of interbreeding species.

evolutionary biology↗

bioRxiv2020

Origins, History and Molecular Characterization ofCreole Cane

Since it was first introduced to Europe in 711 CE and planted in the Americas in 1506, a single type of cane dominated sugar production for 1100 years, until it was finally ousted by Tahitian cane c. 1790. This cane became known as Creolea[A][Z] and is present in the ancestry of many sugarcane hybrids, even today. Whether there was only a single variety of Creole cane or multiple varieties has been a matter of debate for decades. Creole cane remains relevant today, as a Creole cane from Jamaica is the currently chosen lecotype for Saccharum officinarum. In this study we identify 18 historical images of Creole cane, many not previously published. We employ image analyses to characterize the internodes and demonstrate evidence for only a single type of Creole in the new world. Chloroplasts and 45s ribosomal RNA sequences from the cultivar BH10/12 (known to have a Creole female parent) were determined that Java ribbon cane is the historical New World sugarcane known as Creole. We demonstrate that Creole cane is an hybrid and not a single species. Thus S. officinarum has no type specimen. We also sequence a ribbon cane (also known as Guinguam) that appeared in the Caribbean between 1790 and 1810 and demonstrate that this cane was a Sinense type from Java that links back to the work of Rumphinus (1660s).

genomics↗