Filarial parasites of the genus Brugia live in mammals (including humans) and are transmitted between hosts by the bite of a blood-feeding mosquito vector. The infective form for the mosquito is the L1 or microfilariae (Mf) a life cycle stage that is highly adapted for life in the bloodstream of the mammal. Mf are developmentally arrested and undergo no further development until ingested by a mosquito. The link between the progression of the developmental cycle and the transition between hosts implies that the Mf has a mechanism by which it can sense its changing environment. Results in other systems have shown that heat shock factor (HSF) can act as a cellular thermometer directly monitoring temperature and oxidative state. As temperature is one of the major differences between the mosquito and mammalian hosts we are interested in investigating the role of HSF in developmental progression. As the tools for functional genomics do not exist for Brugia, we are using C. elegans as a model system in which to define the role of HSF in a nematode. ACeDB identifies a single HSF-like gene with a highly conserved DNA binding domain. Using an RNAi feeding vector containing fragments of different lengths of C.elegans HSF, we have defined a number of phenotypes. The penetrance of these phenotypes increases with the size of the RNAi fragment and higher growth temperatures. RNAi treated worms have defects in thermotolerance, lifespan, fertility and egg-laying. In addition treated worms are significantly smaller and have a scrawny appearance. In an hsp- 16/GFP reporter background, RNAi abolished GFP expression in the intestine but not in the pharynx or nerve ring. The decrease in HSP-16 levels has been confirmed by immunoblotting. Using a yolk protein/GFP reporter, flourescence in the oocytes is significantly reduced in RNAi treated worms. These results may relate to defects in gut function in RNAi treated worms, and this is consistent with a decreased gut function as defined by feeding assays. Ongoing studies are focused on determining the spatial and temporal expression pattern of hsf throughout development. Our aims are to determine the pathways in which HSF is active under normal developmental conditions and to identify down-stream targets of HSF.