中文摘要
细胞的恶性化是基因突变或缺失导致的一种典型的细胞病。2015年之前的所有有关细胞恶性化(即癌变)的研究都集中在多细胞动物,其中水螅(Hydra)是发现肿瘤的最低等多细胞物种。2015年我们在PNAS发表研究报告指出,单细胞的寄生原生动物也存在恶性化现象[参考文献28]。原生动物恶性化的发现显示恶性化是真核生物古老和固有的生物学现象。但是,没有人知道导致这些寄生原虫恶性化的原因和机理。本项目计划对具有复杂细胞分化能力的布氏锥虫和已失去分化能力的伊氏锥虫(我们认为是布氏锥虫的恶性化虫株,见参考文献8,10)的基因组进行深度比较分析,发现与分化有关的基因,并揭示导致恶性化的机理。研究结果可为研究恶性化(癌症,特别是白血病)起源和演化提供分子证据,并为建立研究相关的细胞模型奠定基础。
英文摘要
Malignancy found in metazoan from Hydra to human is a typical cellular disease caused by the deletion or mutation of the genes. Before 2015, almost all studies on malignancy or cancer were focused on multicellular animals, of them Hydra is the lowest species involved. In 2015, we published a paper in PNAS (USA) regarding cancer in parasitic protozoan[Ref. 28]. The discovery of the malignancy in parasitic protozoans indicated that it is a ancient and inherent biological characteristic in eukaryotes. However, no one knows the reason(s) for causing the malignancy in these protozoan organisms. In this project, we are planning to analyse the differences of genom between Trypanosoma brucei (with various differentiation ability) and T. evansi (which lost differentiation ability and suggested a subspecies or even a strain of T. brucei –see Refs 8 and 10), to find the genes related with differentiation of T. brucei and to reveal the mechanism(s) causing malignancy in this parasite. Results from this project can provide molecular evidence to understanding the origin and evolution of the malignancy particularly leukemia and to establish the related cell model.
