弓形虫可感染几乎所有有核细胞，其引起的弓形虫病尚无理想的治疗药物。宿主细胞被侵袭后能通过自噬降解病原并激活免疫反应。但弓形虫能够逃避细胞自噬甚至利用自噬产生的能量用于自身增殖，目前关于弓形虫与细胞自噬互作的分子机制仍不清楚。本团队前期研究发现弓形虫可激活细胞Raf/MEK/ERK信号通路进而引起自噬，雷帕霉素和氯喹分别对细胞进行处理后，弓形虫胞内增殖也相应地增加和减少，提示其胞内增殖与细胞自噬有密切联系。基于此，本研究拟通过免疫共沉淀、免疫印迹、蛋白质谱、基因条件性沉默等方法进一步研究弓形虫ROPs与Raf/MEK/ERK通路的互作方式，阐明ROPs诱导细胞自噬的信号通路，解释自噬溶酶体对弓形虫增殖的影响，验证Rabs蛋白的表达及定位对弓形虫转运能量的作用。研究结果不仅对探明Raf/MEK/ERK通路调控弓形虫胞内增殖的分子机制具有重要意义，也将为发现新抗虫药靶、研发创新药物等提供新思路。

Toxoplasma gondii (T. gondii) is able to infect almost all nucleated cells and there is no effective therapy for toxoplasmosis right now. After being invaded, cell-autophagy would be induced to degrade pathogens and host immune responses could also be activated at the same time. However, T. gondii could escape cell-autophagy and even use the energy generated for self-proliferation. In previous study, we confirmed that T. gondii invasion could induce cell-autophagy through Raf/MEK/ERK pathway, in addition, after being treated with rapamycin and chloroquineor, the intracellular proliferation of T. gondii increased and decreased respectively. All these results indicated that the proliferation of T. gondii was closely related with the process of cell-autophagy. In this research, co-immunoprecipitation, western blot, protein spectrum analysis and knockdown-strain screening will be applied to verify the specific interaction between T. gondii ROPs and Raf/MEK/ERK pathway. Moreover, we will explore the influences of autolysosome on T. gondii proliferation and illustrate the role of Rabs on energy transportation of T. gondii through western blot, quantitative real-time PCR, immunofluorescence, electron microscope and so on. All together, we will try to paint a blueprint of the whole molecular mechanism of T. gondii proliferation regulated by Raf/MEK/ERK pathway. The results of our study will provide new thoughts for anti-T. gondii drug targets discovery and therapy development.