Brugia malayi is a parasitic nematode that causes lymphatic filariasis, a condition that affects approximately 120 million people, in humans. Mosquitoes transmit B. malayi infective stage larvae (iL3) to humans during a blood meal and disease symptoms occur when adults accumulate in the lymphatic system. Caenorhabditis elegans is an extensively studied free-living nematode whose dauer developmental stage is considered to be similar to the B. malayi iL3 stage. The insulin/IGF-1 signaling pathway (IIS) in C. elegans is known to regulate dauer formation and recovery in response to signals from the insulin receptor, DAF-2, which inhibits dauer formation and is required for dauer recovery. Because there is evidence demonstrating that IIS pathways in C. elegans and parasitic nematodes are conserved, we hypothesize that this pathway in C. elegans will function similarly in B. malayi. To test whether Bma-DAF-2 functions similarly to Ce-DAF-2, we are cloning the Ce-daf-2 promoter and the Bma-daf-2 cDNA into a transgenesis plasmid which will be injected into C. elegans daf-2 mutants to see if it can restore DAF-2 function. If Bma-DAF-2 restores dauer formation in C. elegans, this may give us a model to test for drugs that specifically inhibit the parasite insulin receptor.
