The investigation of parasitic nematode biology has been hampered by the lack of tools for genetic analysis and manipulation. Nematodes of the genus Parastrongyloides have an unusual life history composed of a conventional parasitic life cycle as gastrointestinal parasites and a completely free-living life cycle. The switch between life cycles is determined by environmental conditions (see Grant & Stasiuk, this meeting), so that under appropriate conditions these worms can be maintained indefinitely as free-living nematodes. We have taken advantage of this free-living life cycle to produce transgenic Parastrongyloides trichosuri, a parasite of the Australian brush tail possum. The free living female adult of P. trichosuri is similar to adult C. elegans hermaphrodites: the reproductive anatomy is a central vulva with bilaterally symmetrical gonad arms extending posterior and anterior. The gonad arms a reflexed, with a gonadal syncytium at the distal end of each arm. Transgenic worms were generated by microinjection of DNA into the gonadal syncytium and recovery of transgenic progeny in the F1. Inheritance of the transgene is consistent with the formation of extrachromosomal arrays, as in C. elegans , so that a proportion of progeny from a transgenic mother carry the transgene. Transmission of the transgene occurs in the parasitic as well as the free living life cycle. The transgene expression is low, perhaps a result of silencing, but using a constitutive promoter derived from the P. trichosuri orthologue of the
hsp-1 gene we have also shown expression in both the parasitic and the free-living life cycles. This technology may permit manipulation of the host-parasite relationship and/or the delivery of bioactive proteins to the host by a transgenic worm: we present evidence that a protein encoded by a transgene and expressed during the parasitic life cycle can elicit a biological response from the host infected with the transgenic worms.