Principal Investigator/Program Director (Last, first, middle): Bayne, Christopher, Jeffrey PROJECT SUMMARY/ABSTRACT. This revised proposal seeks support for an investigator-initiated research project into the cellular and molecular means used by intermediate hosts of a human parasite to immunologically attack and kill these parasites. The broad, long-term objective is to break the cycle of parasite transmission to at-risk human populations. The research builds on recent progress in the applicant's laboratory and other laboratories, and exploits the principles of comparative functional genomics and an emerging database for the host snail's genome. In particular, the research deals with genes, messenger RNAs and proteins involved in the cellular respiratory burst ? a complex pathway in which damaging reactive oxygen and nitrogen species are produced by the defense cells of the host and which are at least partialy responsible for the capacity of individual snails to resist infection.
The aims address plausible hypotheses dealing with (i) genes: details of gene structure, transcription and post-transcriptional editing, (ii) proteins (including enzyme activities), (iii) activation pathways for cell responses, and (iv) ultimate causes of death of sporocysts. The hypotheses are both tractable and reasonably anchored in already demonstrated phenomena. Experimental materials include individual Biomphalaria glabrata snails with known susceptible or resistant phenotypes to a standard strain (Oregon PR1) of Schistosoma mansoni, a causative agent of human intestinal schistosomiasis. Funds will enable a team of researchers to focus their efforts on these issues over 5 years. Knowledge resulting from the studies is expected to enhance the likelihood of achieving a mission of this agency - prevention of future transmission of schistosome parasites (S. mansoni) to humans - accomplished by interruption of the parasite's life cycle in its intermediate host, B. glabrata. These goals will be addressed using inbred strains of the intermediate host snail species for which we have the necessary genetic information (nucleic acid sequence data) and in which it is now feasible to use sensitive reporters for and efficient inhibitors of a variety of cell functions. Project Description Page 6

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI016137-21S1
Application #
7486084
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Costero, Adriana
Project Start
1981-09-30
Project End
2008-03-31
Budget Start
2007-07-01
Budget End
2008-03-31
Support Year
21
Fiscal Year
2007
Total Cost
$14,211
Indirect Cost
Name
Oregon State University
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339
Adema, Coen M; Hillier, LaDeana W; Jones, Catherine S et al. (2017) Whole genome analysis of a schistosomiasis-transmitting freshwater snail. Nat Commun 8:15451
Tavalire, Hannah F; Blouin, Michael S; Steinauer, Michelle L (2016) Genotypic variation in host response to infection affects parasite reproductive rate. Int J Parasitol 46:123-31
Tennessen, Jacob A; Bonner, Kaitlin M; Bollmann, Stephanie R et al. (2015) Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni. PLoS Negl Trop Dis 9:e0004077
Tennessen, Jacob A; Théron, André; Marine, Melanie et al. (2015) Hyperdiverse gene cluster in snail host conveys resistance to human schistosome parasites. PLoS Genet 11:e1005067
Larson, Maureen K; Bender, Randal C; Bayne, Christopher J (2014) Resistance of Biomphalaria glabrata 13-16-R1 snails to Schistosoma mansoni PR1 is a function of haemocyte abundance and constitutive levels of specific transcripts in haemocytes. Int J Parasitol 44:343-53
Hoffmann, Christopher J; Ledwaba, Johanna; Li, Jin-Fen et al. (2013) Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Antivir Ther 18:915-20
Yoshino, T P; Bickham, U; Bayne, C J (2013) Molluscan cells in culture: primary cell cultures and cell lines. Can J Zool 91:
Duwell, Monique M; Knowlton, Amy R; Nachega, Jean B et al. (2013) Patient-nominated, community-based HIV treatment supporters: patient perspectives, feasibility, challenges, and factors for success in HIV-infected South African adults. AIDS Patient Care STDS 27:96-102
Blouin, Michael S; Bonner, Kaitlin M; Cooper, Becky et al. (2013) Three genes involved in the oxidative burst are closely linked in the genome of the snail, Biomphalaria glabrata. Int J Parasitol 43:51-5
Svensson, Elin; van der Walt, Jan-Stefan; Barnes, Karen I et al. (2012) Integration of data from multiple sources for simultaneous modelling analysis: experience from nevirapine population pharmacokinetics. Br J Clin Pharmacol 74:465-76

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