Biology subjects

Mim, M. S.

Publications and source records attributed to Mim, M. S..

4 recordsLinked to original sources

bioRxiv2025

CalciumInsights: An Open-Source, Tissue-Agnostic Graphical Interface for High-Quality Analysis of Calcium Signals

Fluctuations and propagation of cytosolic calcium levels at both the cellular and tissue levels show complex patterns, referred to as calcium signatures, that regulate growth, organ development, damage responses, and survival. The quantitative analysis of calcium signatures at the cellular level is essential for identifying unique patterns that coordinate biological processes. However, a versatile framework applicable to multiple tissue types, allowing researchers to compare, measure, and validate diverse responses and recognize conserved patterns across model organisms, is missing. Here, we present a post-processing tool, CalciumInsights, which leverages the R packages Shiny and Golem. This tool has a graphical user interface and does not require software programming experience to perform calcium signal analysis. The open-source software has a modular framework with standardized functionalities that can be tailored for various research approaches. CalciumInsights provides descriptive statistical analysis through various metrics extracted from dynamic calcium transients and oscillations, such as peak amplitude, area under the curve, frequency, among others. The tool was evaluated with fluorescence imaging data from three model organisms: Danio rerio, Arabidopsis thaliana, and Drosophila melanogaster, demonstrating its ability to analyze diverse biological responses and models. Finally, the open-source nature of CalciumInsights enables community-driven improvements and developments for enabling new applications. Author SummaryThis manuscript introduces CalciumInsights, an open-source tool for calcium signature analysis. Designed to be a versatile tool that works with various tissue types and biological systems, CalciumInsights has an easy-to-use graphical user interface. Our program simplifies metrics extraction while maintaining the quality of the analysis by integrating several algorithms. CalciumInsights stands out for its user-friendliness, ease of use, and robust data exploration features, such as tunable filters for improved accuracy. These features promote inclusivity and lower barriers to scientific research by making calcium signature analysis accessible to users of all programming skill levels.

bioengineering↗

bioRxiv2025

Forward Engineering Organ Development and Cancer Therapeutics with Optogenetics

Robust growth control is an essential requirement for the survival of living organisms, while its dysregulation results in diseases such as cancer. However, a significant knowledge gap exists in understanding how precise organ growth control is achieved. The growing arsenal of optogenetic toolkits allows precise, noninvasive control of cellular signaling in vivo, enabling research into how bioelectrical and chemical cues regulate organ growth. Here, we used the red-light-activated channelrhodopsin, CsChrimson, to stimulate intracellular calcium signaling dynamics in the wing epithelium of Drosophila melanogaster, an established model system for investigating organ size control. By varying light intensity and activation dynamics systematically, we identified a biphasic regulation of final organ size. Illumination of CsChrimson depolarizes cells and stimulates spikes of cytosolic calcium concentrations, a phenomenon explained by a computational model that incorporates the inclusion of both gap junction closure and voltage-gated calcium channel activation. This calcium regulation tunes downstream effectors involved in growth regulation and apoptosis. In particular, we found that prolonged bright red light exposure (100 lux/12 hours) increased cell death in wing imaginal discs and caused severe morphological abnormalities in adult wings, with phenotypic severity dependent on stimulation parameters defined by illumination intensity and period of activation. Strikingly, an optimum level of dim, pulsatile light (5 lux, 1 minute on/off pulse train) resulted in overgrown organs and significantly upregulated cell proliferation. We also co-expressed an oncogene, RasV12, with CsChrimson and showed that experimental optical simulation parameters can be exploited to control the morphology of tumorous tissues and initiate targeted remission of tumorous growth. Our findings and approach provide a powerful framework to dissect the role of dynamic physiological signaling events in organogenesis and offer translational insights into new therapeutic strategies with applications in cancer and regenerative medicine.

bioengineering↗

bioRxiv2023

Piezo regulates epithelial topology and promotes precision in organ size control

Mechanosensitive Piezo channels regulate cell division through calcium-mediated activation of ERK signaling or activate Rho signaling to mediate cell extrusion and cell death. However, systems-level functions of Piezo in regulating organogenesis remain poorly understood. Here, we demonstrate that Piezo controls epithelial cell topology to ensure precise organ growth through the integration of live imaging experiments with pharmacological and genetic perturbations and computational modeling. Notably, knockout or knockdown of Piezo led to bilateral asymmetry in wing phenotypes. While pharmacological activation of Piezo stimulated an increase in the frequency of spikes in cytosolic Ca2+, we discovered that Piezo overexpression counterintuitively reduces Ca2+ signaling dynamics. Knockdown of Piezo inhibited proliferation and decreased apoptosis, resulting in an overall increase in epithelial overcrowding. In contrast, either genetic overexpression or pharmacological activation of Piezo increased cell proliferation and cell removal through basal extrusion. Surprisingly, Piezo overexpression increased the hexagonality of cellular topology. To test whether Piezo regulates cell topology, we formulated computational simulations to investigate how expression levels of Piezo protein regulate cell proliferation and apoptosis through modulation of the cut-off tension required for Piezo channel activation. Quantitative analysis validated computational simulation predictions of how perturbations to Piezo impacted epithelial topology. Overall, our findings demonstrate that Piezo promotes robustness in regulating epithelial topology and is necessary for precise organ size control.

developmental biology↗

bioRxiv2022

Balancing competing effects of tissue growth and cytoskeletal regulation during Drosophila wing disc development

Cytoskeletal structure and force generation within cells must be carefully regulated as the developing organ grows to reach a final size and shape. However, how the complex regulation of multiple features of tissue architecture is simultaneously coordinated remains poorly understood. Through iterations between experiments and novel computational multi-scale model simulations, we investigate the combined regulation of cytoskeletal regulation and proliferation in the growing wing imaginal disc. First, we found through experiments and calibrated model simulations that the local curvature and nuclear positioning of cells in the growing wing disc are defined by patterning of nested spatial domains of peaks in apical and basal contractility. Additionally, predictions from model simulations that incorporate a mechanistic description of interkinetic nuclear migration demonstrate that cell proliferation increases the local basal curvature of the wing disc. This is confirmed experimentally as basal curvature increases when growth and proliferation are increased through insulin signaling. In surprising contrast, we experimentally found that Decapentaplegic (Dpp), the key morphogen involved in both growth control and patterning of the anterior-posterior axis, counteracts increases in tissue bending due to cell proliferation via a combined mechanism that balances the competing impacts of both proliferation and patterning of cell contractility. Overall, the high conservation of these regulatory interactions suggests an important balancing mechanism through dual regulation of proliferation and cytoskeleton to meet the multiple criteria defining tissue morphogenesis.

developmental biology↗