The theory of dynamical systems is a way to explain how things change and interact over time. In simpler words, it's like a set of rules that guides how a series of states happen one after another. Usually, we use a bunch of math equations, called differential equations, to describe how each part changes based on what the other parts are doing. We develop mathematical models to simulate and analyze miRNA-mediated gene regulation. Specifically, we modelled and simulated p21 regulation by its targeting miRNAs and showed the miRNA-mediated fine-tuning of the gene expression levels in different cellular processes. We modeled and analyzed miRNA-mediated gene circuits, such as feedback and feedforward loops, to understand the regulatory mechanisms underlying cell cycle regulation and cellular decision-making as well as to predict the impact of extracellular and intracellular perturbations. We modeled the role of miR-205 and miR-342 to decrease chemoresistance of tumor cells through cooperative repressing of E2F1 in cancer cell lines and validated the results in vitro.
MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance
Lai X, Gupta SK, Schmitz U, Marquardt S, Knoll S, Spitschak A, Wolkenhauer O, Pützer BM, Vera J.
Theranostics. 2018;8(4):1106-1120.
We integrate bioinformatics, structural modelling, kinetic modelling, and experiments to find new avenues for overcoming chemotherapy resistance in aggressive tumor cells. Our results show that cooperating miR-205 and miR-342 can reduce E2F1-related chemoresistance in tumor cells.
Understanding microRNA-mediated gene regulatory networks through mathematical modelling
Lai X, Wolkenhauer O, Vera J.
Nucleic Acids Research. 2016;44(13):6019-6035.
We demonstrate that mathematical modeling is a powerful tool to study microRNA-mediated gene circuits and it provides an explanation for non-linear dynamics such as bistability in experimental observations.
Computational analysis of target hub gene repression regulated by multiple and cooperative microRNAs
Lai X, Schmitz U, Gupta SK, Bhattacharya A, Kunz M, Wolkenhauer O, Vera J
Nucleic Acids Research. 2012;40(18):8818-8834.
We develop a workflow combining bioinformatics and mathematical modeling to study target hub gene regulation by microRNAs. We predict and validate that miR-572 and miR-93 efficiently downregulates the expression of p21 in response to DNA damage in vitro. In addition, we elaborate the dynamics of p21 expression in different biological processes.