Abstract
The goal of the present study is to integrate different datasets in cell biology to derive additional quantitative information about a gene or protein of interest within a single cell using computational simulations. We propose a novel prototype cell simulator as a quantitative tool to integrate datasets including dynamic information about transcript and protein levels and the spatial information on protein trafficking in a complex cellular geometry. In order to represent the stochastic nature of transcription and gene expression, our cell simulator uses event-based stochastic simulations to capture transcription, translation, and dynamic trafficking events. In a reconstructed cellular geometry, a realistic microtubule structure is generated with a novel growth algorithm for simulating vesicular transport and trafficking events. In a case study, we investigate the change in quantitative expression levels of a water channel-aquaporin 4-in a single astrocyte cell, upon pharmacological treatment. Gillespie based discrete time approximation method results in stochastic fluctuation of mRNA and protein levels. In addition, we compute the dynamic trafficking of aquaporin-4 on microtubules in this reconstructed astrocyte. Computational predictions are validated with experimental data. The demonstrated cell simulator facilitates the analysis and prediction of protein expression dynamics.
Highlights
Advancements in optical imaging, microscopy, and quantitative techniques in molecular biology allow the measurement of protein expression levels, localization, and dynamic trafficking events in a single cell or a population of cells
The entire “life-story” of a protein including the transcriptional activation of its gene, mRNA generation and processing, translation, transport of the mature protein to its subcellular destination and its eventual degradation dynamics can be measured with different molecular biology techniques
Kinetic parameters shown in Equations (11) to (14) were determined to arrive at physiological aquaporin 4 (AQP4) protein and transcript levels
Summary
Advancements in optical imaging, microscopy, and quantitative techniques in molecular biology allow the measurement of protein expression levels, localization, and dynamic trafficking events in a single cell or a population of cells. With fluorescent tags like quantum dots [3], single molecule tracking of surface proteins [4,5], motor proteins [6,7], and intracellular protein trafficking [8] can reveal spatial trajectories of proteins of interest within a live cell or on the cellular membrane. If these datasets on gene activation, protein expression and dynamic spatial localization can be integrated, it could lead to the prediction of cellular behavior under different conditions. The successful integration of cellular data with spatial information and temporal quantitative measurements by means of a mathematical, mechanistic model of the whole cell can enable the precise prediction of expression level changes in the cellular system
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
