PDCD5调控的细胞凋亡通路的数学模型

Apoptosis occurs during every stages of normal development of multicellular organism. Disregulation in apoptotic pathways plays a causative role in a number of human diseases including cancers. Understanding the molecular mechanism in apoptosis regulations will behelpful in understanding pathogenic mechanisms and developing practical therapeutic methods. One important goal of apoptosis research is to understand how the regulation pathways interact with each other to determine the cell fate decision in response to stimulus. PDCD5 is a proapoptotic molecule who interacts with p53 to regulate apoptosis. Recently, several controversial results on the functions of PDCD5 and its interactions with p53 was reported by Bock et al. These results conflict with previous experiments. This project focus on the controversial results on PDCD5 and p53 via studying the regulatory networks of PDCD5 and p53, which are of great importance in the regulation of apoptosis. We establish mathematical models to investigate the PDCD5 regulated p53 dynamics and cell fate decision and use the model to resolve the controversy and investigate the detailed mechanisms of PDCD5 regulated p53 networks and cell fate decision. In addition, due to the delay in DNA damage and repairing and the importance of delay in the dynamics of the system, we will investigate the role of delays in PDCD5-regulated pathways to understand the mechanism of the regulation of PDCD5. This project emphasizes the integration of biological literature and experimental data. The simulations and analysis of the models focus on the biological pictures. This project provides better understanding of the mechanism of apoptosis regulated by PDCD5 and p53, and provides helpful suggestions on the controversy about PDCD5 and p53 and further experiments.

细胞凋亡是广泛存在的重要生理现象，细胞凋亡的失调会引起癌症等多种疾病。因此理解细胞凋亡对相关疾病及临床治疗的研究具有重大意义。细胞凋亡研究的主要目标之一是了解细胞在受到凋亡刺激后是否启动凋亡程序。PDCD5是重要的促凋亡分子，它和凋亡关键分子p53作用，调控细胞凋亡。但是最近实验报道了与先前诸多实验不同的关于PDCD5的结果。本课题针对此争议，以PDCD5调控p53通路为核心，利用动力学模型，研究PDCD5调控的p53动力学及细胞命运选择，澄清争议并研究PDCD5调控的详细机制。此外，细胞中生化反应的时滞影响着系统的动力学性质，为此本科题将研究时滞对PDCD5调控通路动力学性质的影响。本项目在数学建模的过程中注重以实验结果为依据，注重数值计算和理论分析结论的生物学意义，本项目的顺利开展将促进PDCD5的争议性实验结果的解决，对建模方法和相关实验的开展都具有重要价值。

细胞凋亡是广泛存在的重要生理现象，细胞凋亡的失调会引起癌症等多种疾病。因此理解细胞凋亡对相关疾病及临床治疗的研究具有重大意义。PDCD5是重要的促凋亡分子，它和凋亡关键分子p53作用，调控细胞凋亡。但是最近实验报道了与先前诸多实验不同的关于PDCD5的结果。本课题针对此争议，以PDCD5调控p53通路为核心，利用动力学模型，研究PDCD5调控的p53动力学及细胞选择，澄清争议并研究PDCD5调控的详细机制。此外，细胞中生化反应的时滞影响着系统的动力学性质，因此以本项目为支撑，我们研究了造血系统的动力学，得到了周期性血小板减少症的发生机制和控制措施，并研究了血小板动力学中时滞对于造血系统动力学的影响。本项目在数学建模的过程中注重以实验结果为依据，注重数值计算和理论分析结论的生物学意义，本项目对PDCD5的争议性实验结果的解决提供了一种解释，对建模方法和相关实验的开展都具有重要参考价值。

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