Sc histosomiasis is one of the world's most common neglected tropical diseases, currently infecting over 200 million people, with 90% of cases occurring in tropical Africa. The involvement of freshwater snails as vectors imparts considerable stability to the schistosome life cycle because snails support the prolific production by asexual reproduction of cercariae, the infective stage of the parasite for people. Efforts thus far to control schistosomes in snails have had but limited success. Our work's overall goal is to identify innovative new ways to interrupt the development and transmission of Schistosoma mansoni in its obligatory Biomphalaria snail hosts, especially in the context of the Lake Victoria basin. Rather than to attempt to suppress large snail populations across broad endemic areas, our approach is to find specific ways to target infected snails and the larval stages of schistosomes living within them . Our field studies also constantly remind us of the impact a warming c limate may have on vector snails and the schistosomes developing within them. Building on both lab- and field-based discoveries made in our ongoing funding period, we propose the following new aims: Aim 1. We seek to learn if immune responses we have shown to be relevant to resistance in a lab model, the Neotropical snail B. glabrata and S. mansoni, are also at play in African Biomphalaria taxa in western Kenya. The transcriptomics and other studies we propose will identify novel characteristics of the responses of African snails to schistosome infection and how snail responses to S. mansoni might be affected by warming c limates. Aim 2. We aim to characterize the means whereby larval trematodes, especially ubiquitously common cattle-transmitted amphistomes, suppress and supplant the development of S. mansoni sporocysts in African Biomphalaria taxa . We will use a combination of in vivo and in vitro approaches coupled with transcriptomics, proteomics and metabolomics techniques to address this issue. Aim 3. We hypothesize that shore-dwelling B. sudanica suffers constant exposure to many different trematode species, including S. mansoni, and have developed a generalist immune strategy featuring tolerance to minimize trematode impact. In contrast, a close relative, B. choanomphala, lives in a deepwater refugium from infection, and we predict will show diminished immune responsiveness and lack of tolerance responses upon challenge with trematodes. Our aims all seek to characterize novel ways to interfere with the development of schistosome larval development in snai ls, build a two-way bridge between lab and field studies and will enable us to continue a 30+ year collaboration between biologists at UNM and the Kenya Medical Research Institute, emphasizing training of young scientists in medical malacology. RELEVANCE (See instructions): Schistosomiasis is one of the world's most common neglected tropical diseases. Its resilience is partly due to the reliance of schistosome parasites on freshwater snail vectors that support the production of prolific numbers of human-infective cercariae. We propose to explo it immune resistance mechanisms in snails and the means whereby competing larval trematodes interfere with larval schistosomes in snails to develop needed new means to control transmission of schistosome parasites to people in sub-Saharan Africa. P ROJ EC / P E R FO R M AN C E SI T E(S) (if ad ditional space is need ed , use ProjecU Performance Site Format