环状RNA在基因表达调控过程中作用的理论探索

A large number of biological experiments indicated that circRNA participate in the regulation of many important life processes from different aspects，and closely relate to some complex human diseases. However, circRNA regulatory mechanisms and its biological functions have remained elusive. It is a leading one of the edge in molecular systems biology for the moment. This project will focus on theoretical studies on several scientific hypotheses about the generation and regulation mechanism of circRNA which biologists have been concerning very much. Combined with biological experimental data or evidence, and cross the application of dynamic system theory, information theory, non-equilibrium thermodynamics and other aspects of theory and method, we will focus on: (1) circRNA is generated simultaneously at the early stage of transcription with the precursor RNA or is generated by regulation after transcription. We compare the two kinds of mechanism of quality; (2) comparing the biological functions of different types of circRNA reside inside and outside of the nucleus; (3) the biological characteristics of the corresponding protein in inhibiting the expression of cancer genes after partial circRNA translates into a regulatory protein. Through these studies, we attempt to reveal the essential mechanism of circRNA formation and to clarify the essential role of circRNA in gene expression. The related research not only helps us to understand the formation mechanism of circRNA and its biological functions, but also helps to understand the pathogenesis of human complex diseases.

大量实验研究表明：环状RNA在多个层面上参与重要生命活动的调控，并与人类复杂疾病密切相关。环状RNA的调控机制及其生物学功能由于其重要性且无定论因此成为系统生物学的研究前沿之一。本项目将针对生物学家目前非常关注的环状RNA生成方式与调控机制的科学假设开展理论探索。将结合生物学实验数据或证据，并交叉运用动力系统理论、信息论、非平衡热力学等方面的理论和方法，重点研究：1, 环状RNA是在转录前期与前体RNA同时生成还是在转录后由调控生成的机制，并比较优劣性；2，不同类型的环状RNA在细胞核内外驻留方式的生物学功能，并找出差异性；3，部分环状RNA翻译成功能蛋白在抑制癌症基因表达方面的生物学特性。通过这些研究，试图揭示出环状RNA生成的本质机制和阐明环状RNA在基因表达过程中的本质作用。相关研究不仅有助于理解环状RNA的调控机制和生物学功能，而且有助于理解人类复杂疾病的致病机理。

大量研究事实表明，随机动力系统相关领域的发展，在现实生活中有着广泛的应用。基于此，为了进一步清晰的理解基因表达动力系统中，基因表达稳定性以及能量耗散的关系，同时在当前一个时期，新冠疫情大流行的阶段，精准刻画传染病的传播机制，本研究将随机动力系统的只是应用到两个层面：基因表达层面：提出一种新的基因表达模型不同阶段的刻画模式，将整个系统分解成两个部分，单独考察基因表达的稳定性与能量耗散，此外，对于能量耗散在不同子块之间的对应关系进一步加以区分；传染病动力学刻画层面：1）构建全新的疾病传染模型，将精细化的种群结构纳入考察的范畴；2）将随机最优控制理论引入疾病传播网络，为有效控制疾病传播提供理论支撑；3）在常规传染病的基础上引入分数阶微分方程模型，进一步精准刻画疾病传播动力学的复杂性。借助随机动力系统方面相关的理论研究基础，将这一理论分析应用于以上两个方面，从数据驱动层面，深层次揭示了基因表达的动力学，此外在随机传染病层面，准确刻画了疾病传播的动力学特征，同时提供了最佳的防控治疗手段，为实施传染病的精准防控奠定了相关的研究基础。