Bcl-xL、Bax、tBid都属于Bcl-2家族，Bcl-xL抑制细胞凋亡，而Bax、tBid促进凋亡；Bcl-xL、Bax能在线粒体上形成膜通道，调控细胞色素c的释放。本课题采用单分子荧光技术，研究Bcl-xL、Bax、tBid的相互作用、构象变化和寡聚行为。具体来讲，我们将研究Bcl-xL、Bax、tBid在溶液和膜环境中的相互作用；tBid是否采取"Hit-and-Run"的方式激活Bax；Bcl-xL、Bax在形成膜通道过程中的构象变化；Bcl-xL、Bax膜通道在聚集状态上的差异；Bcl-xL是否结合膜上的Bax并将其转移到溶液中；如果Bcl-xL能将膜上的Bax转移到溶液中，那么之后，两者是继续保持结合，还是各自以单体的形式存在于溶液中。显然，找到这些问题的答案将有助于阐明Bcl-2家族蛋白调控细胞凋亡的机制，对于Bcl-xL、Bax的抑制剂设计也有着重要意义。

Bcl-xL, Bax and tBid belong to Bcl-2 family. Bcl-xL inhibits the apoptosis while Bax, tBid promote the process. Both Bcl-xL and Bax may form pores in mitochondria and regulate the release of cytochrome c. Here we will study the interaction, conformational change and oligomerization of Bcl-xL, Bax and tBid by single molecule fluorescence technology. Specifically, we are going to study the interactions among Bcl-xL,Bax,tBid in solution and in membrane, the conformational change of Bcl-xL and Bax during their pore formation, the structural difference of Bcl-xL, Bax pores. Also, we will answer the questions such as: whether tBid activates Bax in a one step, "Hit-and-Run" manner；whether Bcl-xL interacts with the membrane-bound Bax and translocates Bax from membrane into solution. If Bcl-xL could translocate Bax into solution, would they keep as a complex or be separated as monomers in solution? Obviously, finding the answers of these questions will not only help elucidate the mechanism of how Bcl-2 family proteins regulate the apoptosis, but also aid the inhibitor design of Bcl-xL and Bax proteins.