细菌在自然界通常以生物被膜的形式存在。生物被膜是铜绿假单胞菌耐受恶劣环境以及产生耐药性的重要原因。生物被膜的发育受到第二信使分子c-di-GMP的严格调控。细胞内的c-di-GMP受体感受细胞内c-di-GMP浓度并将信号向下游传递，产生多种生理效应。例如生物被膜的形成以及毒力因子的表达。本项目计划系统地测定铜绿假单胞菌中的三种重要的c-di-GMP受体（FleQ,PilZ与Alg44）的晶体结构，并结合生物化学与微生物学实验在分子水平上阐明c-di-GMP的浓度信号如何进一步作用于下游的信号通路，特异的调控细菌的生理功能。

Bactera generally exist as biofilm in natural enviroment. Biofilm formation is an important reason for Pseudomonas aeruginosa to aquire drug resistance. The development of biofilm is tightly controled by the secondary messenger c-di-GMP.The intracellular c-di-GMP receptors sense the concentration of c-di-GMP and transduct the signals downstreams and induce various physiological functions such as biofilm formation and virulence factor expression. We plan to systematically determine three c-di-GMP receptors (FleQ, PilZ and Alg44) of Pseudomonas aeruginosa. And the structures combined with biochemical and microbiological data will be used to elucidate how the concentration of c-di-GMP acts on the downstream signaling pathways and regulate bacterial behaviour specifically.