基于贾第虫的极小基因组探索构建简约基因组和真核底盘细胞

合成生物学被认为是认识生命的钥匙和改变未来的颠覆性技术。构建底盘细胞是其中重要的一环。目前构建的底盘细胞不多且多为原核型的。而真核底盘细胞因有其不可替代的优势而需求十分迫切。但苦于许多真核细胞基因组大而复杂，在构建底盘细胞过程中要去掉原有基因组中的非必需基因（成为简约基因组）难度极高。根据构建底盘细胞需满足的条件和我们长期对单细胞原生动物贾第虫的研究积累，认为蓝氏贾第虫具有构建底盘细胞的独特优势：其基因组因寄生适应进化而高度缩减（仅12.6Mb，基因数、内含子、重复序列等均很少），且能独立于宿主进行长期培养。本项目就是拟以研究背景最清楚的蓝氏贾第虫WB株为材料，利用在贾第虫上已成功建立的基因组编辑技术对其在培养条件下的非生存必需的基因（如许多寄生适应性基因等）进行删减，构建出具简约基因组的简约细胞，然后再设计构建具有特色的底盘细胞。该研究具有显著的创新性和重要的基础研究和实际应用意义。

Synthetic biology is considered as the key to understanding life and a paradigm-shifting technology changing the future. The reconstruction of chassis cells is the most important part of it. Up to now, some chassis cells have been constructed but most of them are prokaryotic. Due to the irreplaceable advantages of eukaryotic chassis cells in generating functional products, it is very urgent to construct eukaryotic chassis cells. However, due to the large-size and complexity of many eukaryotic genomes, the deletion of non-essential genes from many eukaryotic genomes is rather difficult. Based on the criteria for chassis cells and our long-term study on unicellular protist Giardia, we propose that Giardia lamblia has unique advantages for constructing chassis cells: its genome has undergone massive reduction for parasitic adaptation (genome size is only 12.6Mb, the numbers of genes, introns, and repetitive sequences all are small or few), moreover, it can be cultivated in laboratory, dependent of the vertebrate hosts. The present project is aimed to reconstruct Giardia minimal genome from G. lamblia WB ATCC 50803, whose genetic background is well known. We plan to delete non-essential genes (such as many genes indispensable for parasitic life) under cultivation circumstance utilizing the well-established genome editing technology in Giardia, and ultimately reconstruct the Giardia minimal cell with minimal genome (genome with the almost smallest gene number). Then based on the minimal cell different Giardia chassis cells will be designed and generated according to different purposes. This project is remarkably innovative and of significance to both basic research and practical application.