小分子热休克蛋白（small heat shock proteins，sHSPs）广泛地存在于各种生物，与其它热休克蛋白家族Hsp60、Hsp70、Hsp90、Hsp100一起组成经典的分子伴侣蛋白系统，对细胞内的其它蛋白质进行广义的“质量控制”。在过去的十多年间,申请人系统地研究了来自细菌的小分子热休克蛋白的生物学功能和作用机制，取得了一定的进展。本项目拟在多年工作的基础上，系统研究线虫小分子热休克蛋白（以Hsp17和Hsp12s亚家族为代表）的生物学功能和作用机制，特别是其延长线虫寿命的分子机制。我们将使用新的生化研究手段（如活体线虫化学交联、变性亲和层析等），鉴定和Hsp17/Hsp12s相互作用的蛋白，系统地研究Hsp17/Hsp12s与关键蛋白因子相互作用的机制及其对寿命的影响。在此基础上，发展基于调控小分子热休克蛋白作用网络实现延长线虫寿命的新方法。

Small heat shock proteins (sHSPs) are widely found in a variety of organisms, and together with such heat shock protein families as Hsp60, Hsp70, Hsp90 and Hsp100 comprise the classic molecular chaperone protein system to monitor the general quality control of other proteins in cells. In the past more than 10 years, the applicant systematically studied the biological function and mechanism of bacterial sHSPs and made some progress. The present project is designed to study the biological function and mechanism of sHSPs from C. elegans (represented by Hsp17 and the Hsp12s subfamily), in particular dissecting the molecular mechanism underlying their lifespan-extension action in worms. To this end, we will apply new biochemical research tools (such as chemical crosslinking in living worms and affinity chromatography under denaturing conditions) to identify the Hsp17/Hsp12s-interacting proteins, and delineate the mechanism of the interactions between Hsp17/Hsp12s and those key protein factors regarding the effect on lifespan. On the basis of these, we aim to develop new methods for lifespan extension in C. elegans through regulating the sHSPs-related protein interaction network.