Biology subjects

Kannan, H.

Publications and source records attributed to Kannan, H..

4 recordsLinked to original sources

bioRxiv2025

CTG clade-specific proteins of the RSC chromatin remodeling complex regulate cell cycle progression of a critical priority fungal pathogen, Candida albicans

The RSC and the homologous chromatin remodeling complexes are known to regulate cell cycle progression in various organisms, including Saccharomyces cerevisiae, Drosophila, and Homo sapiens. In this work, we characterized the role of two novel CTG clade-specific proteins (Nri1 and Nri2) of the RSC complex in the regulation of cell cycle progression in a critical priority fungal pathogen, Candida albicans. We observed that Nri1, alone or along with Nri2, regulates cell cycle progression at multiple stages. The nri1{Delta}/{Delta} and nri1{Delta}/{Delta} nri2{Delta}/{Delta} mutants exhibited transient cell cycle arrest, defective spindle morphology, and cytokinesis. Transcriptomic analysis supported these mutant phenotypes and indicated a broad role of Nri proteins in the cell cycle. From our results, we conclude that Nri proteins are crucial for C. albicans proliferation and fitness. ImportanceThe composition of the essential RSC chromatin remodeling complex exhibits species-specific divergence, harboring unique subunits with distinct functions. In this study, we report that two fungal CTG clade-specific proteins of the C. albicans RSC complex, namely Nri1 and Nri2 can promote C. albicans fitness through regulating its cell cycle progression at multiple stages. Fitness defect along with stressor sensitivity and differential expression of the genes regulating pathogenesis in the nri mutants indicate potentiality of the Nri proteins as anti-Candida drug targets.

cell biology↗

bioRxiv2025

A microfluidic gradient and parallel-track system uncovers spatial control of endocytosis and adhesion formation in breast cancer cell migration

Cell migration through confined spaces is a critical step in cancer metastasis, yet the spatial regulation of endocytosis and adhesion dynamics during this process remains poorly understood. To address this, we developed a microfluidic platform that generates stable, spatially linear biochemical gradients across 5 m-tall migration channels while limiting confounding flow-induced shear stress (<0.05 dyn/cm2). COMSOL simulations and optical calibration using FITC-dextran confirmed that gradients form reliably within 5 minutes. The microdevice also supports long-term live imaging and is compatible with both spinning disk confocal and total internal reflection fluorescence structured illumination microscopy modalities, enabling high-resolution visualization of adhesion and endocytic structures. Localized application of the endocytic inhibitor Dyngo-4a to the front or rear of migrating cells revealed that front-targeted inhibition significantly increased the enrichment of paxillin and the clathrin adaptor AP-2 at the leading edge, whereas rear-targeted inhibition completely abolished their front-rear asymmetry. These changes were accompanied by enhanced migration speed and persistence, particularly under front-targeted inhibition. Together, these findings highlight the critical role of spatially coordinated endocytosis in sustaining polarized adhesion and persistent cell movement. Our platform offers a powerful tool for dissecting subcellular mechanisms of migration under confinement and provides a broadly applicable framework for probing spatially localized signaling in engineered microenvironments.

cell biology↗

bioRxiv2025

Chemosensory Adaptations in Caenorhabditis Males during the Establishment of Androdioecy.

Caenorhabditis elegans has evolved from its dioecious ancestors to adopt an androdioecious reproductive strategy. In this process, ancestral female C. elegans acquired genetic modifications that enabled self-sperm generation, self-sperm activation, and a reduced reliance on sexual reproduction. However, how males have adapted during this transition from dioecy to androdioecy is less explored. Using respective Caenorhabditis species, we demonstrated that androdioecious hermaphrodites exhibit a reduction in sex pheromone potency, while androdioecious males show notably heightened olfactory habituation and diminished mate exploration capabilities. The behavior of androdioecious males can be reverted to resemble that of dioecious males by replacing the SRD-1 receptor with its dioecious orthologs. This intrinsic characteristic is contingent upon the cytoplasmic domain of the receptor. We propose a theoretical framework where C. elegans males have accumulated genetic variations in their pheromone receptor, leading to altered chemosensory perception of the opposite sex, which confer a selective advantage that favors the establishment of hermaphroditism. Our study provides insights into an overlooked male trait that was shaped by changes in chemosensory signaling. The findings underscore the capacity of chemosensory variations to influence how organisms perceive critical ecological factors and eventually facilitate the emergence and stabilization of hermaphroditism.

evolutionary biology↗

bioRxiv2023

Spatiotemporal development of growth and death zones in expanding bacterial colonies driven by emergent nutrient dynamics

Bacterial colony growth on hard agar is commonplace in microbiology; yet, what occurs inside a growing colony is complex even in the simplest cases. Robust colony expansion kinetics featuring a linear radial growth and a saturating vertical growth indicates a common developmental program which is elucidated here for Escherichia coli cells using a combination of modeling and experiments. Radial colony expansion is found to be limited by mechanical factors rather than nutrients as commonly assumed. In contrast, vertical expansion is limited by glucose depletion inside the colony, an effect compounded by reduced growth yield due to anaerobiosis. Carbon starvation in the colony interior results in substantial cell death within 1-2 days, with a distinct death zone that expands with the growing colony. Overall, the development of simple colonies lacking EPS production and differentiation is dictated by an interplay of mechanical constraints and emergent nutrient gradients arising from obligatory metabolic processes.

microbiology↗