基于组学策略的贾第虫能量代谢通路研究

Giardia is one of the most primitive ,unicellular eukaryotic model biology and also is the important intestinal parasitic protozoa. Its metabolism and energy production have been a hot research topic. In our previous study, Giardia transcription library was constructed and sequenced. The metabolism enzymes involved in carbohydrates, amino acids and lipid metabolism were screened to reconstruct metabolic pathways. On the basis of that, the project intends to adopt transcriptomics and metabolomics as search tools.The whole data of omics and experimental study will be intergrated to analysis the relationship between metabolism of carbohydrates, amino acids and lipids and energy production in Giardia trophozoites under different culture conditions and to build the energy metabolic network of Giardia. The metabolites difference between Giardia trophozoites will be tested and the corresponding metabolic pathway will be examinated. Based on the analysis of the transcription factors and the energy metabolic flux during Giardia morphological change from trophozoites to cysts , we will explore the conversion mechanism and mode of energy metabolism pathway. The metabolic study of the infected model by Giardia will be carried to dissect the interactions between host and Giardia. The results will provide worthy experimental data for interpreting energy metabolism of Giardia protozoan and provide a new idea for the evolution study of eukaryotic metabolism represented by Giardia. These studies are also be observed to evalute potential drug for treating Giardia infection and to provide the basis for early diagnosis of giardiasis.

贾第虫是最原始的单细胞真核模式生物，也是重要的肠道寄生原虫。其代谢的发生与能量产生一直是研究热点。课题组前期通过贾第虫转录文库构建与测序，筛选出与碳水化合物、氨基酸和脂类代谢有关的酶，对代谢通路进行重构。在此基础上，本项目拟采用转录组学和代谢组学方法，整合分析不同培养条件下贾第虫滋养体碳水化合物、氨基酸和脂类等代谢与能量产生的关系，构建贾第虫能量代谢网络；对比分析不同培养条件下贾第虫滋养体的差异代谢产物，鉴定相关代谢通路；通过转录调控因子的筛选和虫体形态改变时能量代谢流量分析，探讨能量代谢通路转换方式与机制；通过感染模型代谢组学研究，揭示贾第虫感染与宿主的相互作用。本研究将为全面阐述贾第虫的能量代谢通路及其转换机制，提供有价值的数据和资料；为以贾第虫为代表的真核生物代谢的进化研究提供新思路；同时为抗贾第虫新药靶点的发现和贾第虫病的早期诊断提供依据。

本项目采用蛋白组学和修饰组学策略，整合分析糖饥饿培养条件2-羟基异丁酰化和乙酰化修饰组学的动态数据变化，探讨碳水化合物、氨基酸和脂类等代谢与能量产生的关系，构建了贾第虫能量代谢网络；通过染色体蛋白组学技术，分析滋养体成囊过程中抗原及能量代谢通路的转换。上述研究阐明了模式真核生物贾第鞭毛虫乙酰化和2-羟基异丁基化调节参与能量代谢转换调节的机制；同时，蛋白质的泛素化及HSPs的调控对贾第虫骨架蛋白的转换具有重要的作用。本研究将为全面阐述贾第虫的能量代谢通路及其转换机制，提供有价值的数据和资料；为以贾第虫为代表的真核生物代谢的进化研究提供新思路；同时为抗贾第虫新药靶点的发现和贾第虫病的早期诊断提供依据。