MicroRNA时空特异性表达在神经干细胞分化中的复杂动力学研究

研究发现microRNA(miRNA)参与神经干细胞分化调控时呈现出时空特异性表达的特性，在神经退行性疾病、脑肿瘤发展过程中发挥重要调节作用。Science杂志两次把miRNA归结为重大科学研究课题。本项目拟以神经系统基因表达数据为基础，根据miRNA时空特异性表达特征，构建神经干细胞分化的基因调控网络，识别提炼重要网络模体、功能模块和信号通路。结合生化反应及生物实验结果，借助计算机软件，构建基于复杂网络的偏微分方程组时空动力学模型。用复杂网络、动力学和控制理论研究其网络拓扑结构及多种重要动力学行为，重点讨论miRNA时空特异性表达对应的网络结构演化特征和基于动态网络的动力系统多稳态和分叉性质，同时考虑时滞因素和扩散效应的影响。并用这些研究结果解释miRNA时空特异性表达对神经干细胞分化生物开关的重要调控机制，以及在神经系统退行性疾病中的调控机制，最终提出相应的调控策略。

Recent biology researches indicated that microRNA(miRNA) showed spatiotemporal specific expression characteristics when participating in the regulation of neural stem cell differentiation, and played an important regulatory role in the development of neurodegenerative diseases and brain tumors. The journal Science has twice identified miRNA as a major scientific research topic. Based on the gene expression data of the nervous system and spatiotemporal specific expression characteristics of miRNA, this project will construct neural stem cell gene regulatory network, and identify important network motifs, functional modules and signaling pathways. Then, a spatiotemporal dynamic model based on complex network and constructed by partial differential equations will be proposed via computer software combined with biochemical reactions and the results of biological experiments. The network topology and various important dynamic behaviors will be studied by complex network and dynamics and control theory. This project will focus on the evolution characteristics of the network structure corresponding to the spatiotemporal specific expression of miRNA and the multi-steady-state and bifurcation properties of the dynamic system based on the dynamic network, while considering the time-delay factor and the diffusion effect. Finally, the important regulatory mechanisms of miRNA spatiotemporal specific expression on neural stem cell differentiation and neurodegenerative diseases will be explained and corresponding regulation strategy will be proposed according to the above theoretical results.