Biology subjects

Priya, P.

Publications and source records attributed to Priya, P..

5 recordsLinked to original sources

bioRxiv2026

Cfap410a and Cby work together with tissue-specific requirements to build Drosophila ciliary transition zones

Cilia and flagella perform essential physiological functions in eukaryotes, and defects in these organelles cause several human diseases, including cancer and ciliopathies. The architecture of cilia is highly organized. The ciliary compartment is separated from the cytoplasm by the transition zone (TZ). The severity of ciliopathies linked to TZ assembly defects highlights the TZ's critical role. Although several core conserved complexes are involved in TZ assembly, variations in TZ composition are associated with structurally and functionally diverse cilia. Here, we identify Cfap410a as a novel component of the ciliary TZ in the two Drosophila ciliated tissues, male germ cells and sensory neurons. Cfap410a is one of the two Drosophila paralogs (Cfap410a and Cfap410b) of human CFAP410, whose mutations are associated with axial spondylo-metaphyseal dysplasia, retinitis pigmentosa and amyotrophic lateral sclerosis. We show here that Cfap410a is a proximity partner of Cby and that they act cooperatively in the hierarchy of the TZ assembly program by bridging the CEP290 and MKS transition zone modules. Simultaneous loss of Cfap410a and Cby halts ciliary growth by disrupting TZ formation in multiple types of Drosophila ciliated cells, each of which exhibiting varying dependence on these two proteins. Interestingly, the function of Cfap410a and Cfap410b are not functionally redundant, indicating that the two proteins have evolved towards specific functions. In summary, our results propose a novel role for CFAP410a at the TZ and provide an explanation for how deregulation of conserved TZ components could lead to tissue-specific ciliopathies.

cell biology↗

bioRxiv2026

Centrosome maintains the integrity of and repairs mature olfactory cilia in adult Drosophila

Mechanisms of cilium assembly are well studied; however, how mature metazoan cilia maintain their structures and functions in vivo remains unknown. It is also unclear whether the centrosome-derived basal body (BB) directly contributes to ciliary homeostasis. We combined biochemistry, genetics, high-resolution subcellular imaging, and electrophysiology to investigate long-lived ciliated olfactory sensory neurons (OSNs) and their olfactory behaviour in adult Drosophila. Several centrosome assembly proteins are absent, but another subset persists through dynamic protein exchange at the BBs of mature olfactory cilia. At this ciliary base, pericentriolar material (PCM) components, e.g., {gamma}-Tubulin23C, centrosomin, and pericentrin-like protein form an interconnected network required for ciliary maintenance. Adult- and OSN-specific depletions of these proteins, particularly in combination, disrupt accumulation of the heterotrimeric kinesin-2 at the ciliary base and, subsequently, in the shaft, causing loss of ciliary tubulin, EB1, and odorant receptor co-receptor. These dysregulations cause profound loss of ciliary shaft and impair olfactory function/behaviour. The centrosomal kinases PLK1/POLO and Aurora A also work with this PCM network and are required for mature ciliary homeostasis. Remarkably, these defects in ciliary structure, function, and adult olfactory behaviour are reversible, suggesting that this centrosome-derived BB is a dynamic homeostatic epicentre that regulates trafficking and ciliary structural and compositional integrity in vivo. These findings uncover an active, centrosome-dependent, cell-autonomous mechanism for maintaining and repairing mature metazoan cilia in fully grown organs in adulthood and also provide a possible explanation for how deregulation of conserved ciliary base components could lead to progressive, late-onset cilia-related disorders.

cell biology↗

bioRxiv2024

PHALCON: phylogeny-aware variant calling from large-scale single-cell panel sequencing datasets

Single-cell sequencing (SCS) enables variant detection and tumor phylogeny reconstruction for resolving intra-tumor heterogeneity (ITH), which causes drug resistance and cancer relapse. Recently emerged panel sequencing methods sequence disease-specific genes across thousands of cells, but existing variant callers and SCS-specific phylogenetic methods struggle with large-scale datasets and amplification biases in panel-based sequencing protocols. We present a statistical variant caller, PHALCON for scalable mutation detection from large-scale single-cell panel sequencing data by modeling tumor evolution under a finite-sites model along a clonal phylogeny. Across a wide variety of simulation settings, PHALCON outperformed state-of-the-art methods in variant calling, tumor phylogeny inference, and runtime. From triple negative breast cancer (TNBC) and acute myeloid leukemia (AML) datasets, PHALCON detected novel somatic mutations with high functional impact, resolved clonal substructure and rare clones. In AML, PHALCON also uncovered poor-survival subgroups harboring DNA methylation and chromatin/cohesin mutations and revealed novel cellular co-occurrence and exclusivity patterns of driver mutations.

bioinformatics↗

bioRxiv2022

Stress Combinations and their Interactions inPlants Database (SCIPDb): A one-stop resource for understanding combined stress responses in plants

We have developed Stress Combinations and their Interactions in Plants Database (SCIPDb; http://www.nipgr.ac.in/scipdb.php), a compendium and interactive platform offering information on both morpho-physio-biochemical (phenome) and molecular (transcriptome) responses of plants to different combinations of stresses. To delineate the effects of various stress combinations/categories on yield in major agricultural crops, global phenome data from 939 studies was analyzed and results showed that yield was affected to the greatest extent under the abiotic-abiotic stress category, followed by the biotic-biotic and abiotic-biotic stress categories. In the abiotic-abiotic stress category, drought-heat, heat-salinity, and ozone-UV are the major stress combinations causing high yield loss in barley, wheat, soybean, and quinoa crops. In the abiotic-biotic stress category, the salinity-weed stress combination causes highest yield loss in rice crop. In the biotic-biotic stress category, the nematode-fungus combination was most detrimental, causing considerable yield losses in potato, groundnut, and sugar beet crops. Transcriptome datasets from 36 studies hosted in SCIPDb identified novel genes. Thus far, these genes have not been known to play a role in combined stress. Integretome analysis under combined drought-heat stress pinpointed carbohydrate, amino acid, and energy metabolism pathways as the crucial metabolic, proteomic, and transcriptional components in plant tolerance to combined stress. These examples illustrate the application of SCIPDb in identifying novel genes and pathways involved in combined stress tolerance. Further, we showed the application of this database in identifying novel candidate genes and pathways for combined drought and pathogen stress tolerance in Arabidopsis and chickpea. To our knowledge, SCIPDb is the only publicly available platform that provides extensive information and paves the way for advancing mechanistic understanding of plant responses to combined stresses.

plant biology↗

bioRxiv2022

A strategy to optimize the peptide-based inhibitors against different mutants of the spike protein of SARS-CoV-2

SARS-CoV-2 virus has caused high-priority health concerns at a global level. Vaccines have stalled the proliferation of viruses to some extent. Yet, the emergence of newer, potentially more infectious, and dangerous mutants such as delta and omicron are among the major challenges in finding a more permanent solution for this pandemic. The effectiveness of antivirals Molnupiravir and Paxlovid, authorized for emergency use by the FDA, are yet to be assessed at larger populations. Patients with a high risk of disease progression or hospitalization have received treatment with a combination of antibodies (antibody-cocktail). Most of the mutations leading to the new lineage of SARS-CoV-2 are found in the spike protein of this virus that plays a key role in facilitating host entry. The current study has investigated how to modify a promising peptide-based inhibitor of spike protein, LCB3, against common mutations in the target protein so that it retains its efficacy against the spike protein. LCB3 being a prototype for protein-based inhibitors is an ideal testing system to learn about protein-based inhibitors. Two common mutations N501Y and K417N are considered in this work. Using a structure-based approach that considers free energy decomposition of residues, distance, and the interactions between amino acids, we propose the substitutions of amino acid residues of LCB3 inhibitors. Our binding free energy calculations suggest a possible improvement in the binding affinity of existing inhibitor LCB3 to the mutant forms of the S-protein using simple substitutions at specific positions of the inhibitor. This approach, being general, can be used in different inhibitors and other mutations and help in fighting against SARS-CoV-2.

biophysics↗