The George Washington University, USA.
I have worked on schistosomiasis related research since 1982 and during this period have worked on molecular aspects of the causative schistosome parasite, Schistosomamansoni, as well as the intermediate snail host, Biomphalariaglabrata. In the parasite, the focus of my research was identifying antigens of the larval schistosomula and adult worm stages for vaccine development. In the snail host, my laboratory initiated studies that successfully described genetic variations between parasite resistant and susceptible snails. These investigations led to the first publication showing heritability of markers for the schistosome refractory phenotype in B. glabrata. My lab, in collaboration with the then TIGR institute, also initiated studies that made use of cDNA libraries generated from a variety of tissues (hemocytes, hepatopancreas, albumen gland, ovotestis, cerebral ganglia) to assess differences in transcriptomic profiles between resistant and susceptible snails. Work in my lab recently led to the discovery that early stress induction culminating in the expression heat shock proteins, such as Hsp 70 and 90 in juvenile snails is a significant aspect of snail susceptibility to S. mansoni. In collaboration with Dr Joanna Bridger at Brunel University, UK we were also the first to discover spatial epigenetics in the snail host schistosome relationship. My current research interest in the Brindley lab at the George Washington University is to develop transgenesis technology in the B. glabrata embryonic (BGE) cell line, enabling us to dissect mechanisms that can be disrupted to block the parasite’s development in the snail host.
Schistosomiasis a major Neglected Tropical Disease (NTDs) that remains difficult to control. Its recent reemergence in Corsica, France confirms its spread from Africa to higher latitudes. Freshwater snails are obligate hosts for development of asexual stages of the trematode that causes schistosomiasis in the tropics and subtropics. Lately, it has been reported that a Mass Drug (praziquantel) Administration (MDA) approach alone to control schistosomiasis has had little impact in curtailing transmission in endemic countries. Without a vaccine to prevent schistosomiasis and this realization that drugs alone will not deliver the global eradication of schistosomiasis, there is impetus for alternative methods to control schistosomiasis, focusing on blocking transmission in the snail. Towards this end, we adopted a molecular approach to identify mechanism(s) that underlie the snail/schistosome interaction. By using resistant and susceptible Biomphalaria glabrata snails infected with Schistosoma mansoni, differences in early gene expression in genetically resistant (BS90) and susceptible (NMRI) snails were investigated. Several genes were differentially expressed between the snail phenotypes. Among others, the stress genes encoding Hsp70 and Hsp 90 were significantly expressed in NMRI (susceptible) compared to the BS90 resistant snails. Intriguingly, snails that was resistant at room temperature when subjected to heat shock at 32oC for 3hours were rendered susceptible. Moreover, the Hsp90 inhibitor geldenamycin rendered susceptible NMRI snails as resistant as BS90. The implications of these data within the context of global warming and the snail vector approach to reduce schistosomiasis will be discussed.
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