The long term objective of the Physician Scientist Award application is to develop an independent biomedical research career in cellular biology and apply this subspecialty to the study of schistosomiasis. Phase I will consist of 2 major divisions. First, a fundamental background in cell biology will be developed utilizing graduate school courses, seminars, journal clubs and informal discussions. A committee will oversee the progress of the candidate. Second, a research project on the biology of surface maturation of Schistosoma mansoni will be initiated under Drs. Kenneth Miller and G. Richard Olds of Brown University. These studies will investigate surface maturation during the transformation of infective cercariae to larval schistosomula, a critical period when the parasite must adapt from a free-living to a parasitic existence. First, the role of second messengers in initiation of surface maturation will be investigated. Next, since microtubule inhibitors prevent surface maturation and reduce the ability of schistosomula to mature into adult worms, microtubules will be studied in depth. Finally, schistosomula surface antigens will belocalized within cercariae using immunocytochemistry. Detection of antigens within cercariae may suggest that vaccines against schistosomiasis could be prepared from the cercarial stage. At the completion of 2 years the candidate will have developed basic skills and education to pursue independent research during Phase II. This research will be a continuation of the study of schistosomes surface membranes. Understanding the cell biological mechanisms of membrane maturation during the cercarial-schistosomula transformation may allow development of new strategies to interrupt transmission of schistosomiasis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Physician Scientist Award (K11)
Project #
5K11AI000780-05
Application #
3085155
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1988-09-30
Project End
1993-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Miriam Hospital
Department
Type
DUNS #
039318308
City
Providence
State
RI
Country
United States
Zip Code
02906
Cochrane, R; Clark, R B; Huang, C K et al. (2001) Differential regulation of T cell receptor-mediated Th1 cell IFN-gamma production and proliferation by divergent cAMP-mediated redox pathways. J Interferon Cytokine Res 21:797-807
Wiest, P M; Dong, K L; Johnson, J H et al. (1994) Effect of colchicine on microtubules in Cryptosporidium parvum. J Eukaryot Microbiol 41:66S
Wiest, P M; Kunz, S S; Miller, K R (1994) Activation of protein kinase C by phorbol esters disrupts the tegument of Schistosoma mansoni. Parasitology 109 ( Pt 4):461-8
Wiest, P M; Johnson, J H; Flanigan, T P (1993) Microtubule inhibitors block Cryptosporidium parvum infection of a human enterocyte cell line. Infect Immun 61:4888-90
Wiest, P M; Li, Y N; Burnham, D C et al. (1992) Schistosoma mansoni: characterization of phosphoinositide response. Exp Parasitol 74:38-45
Wiest, P M; Li, Y; Olds, G R et al. (1992) Inhibition of phosphoinositide turnover by praziquantel in Schistosoma mansoni. J Parasitol 78:753-5
Wiest, P M; Burnham, D C; Olds, G R et al. (1992) Developmental expression of protein kinase C activity in Schistosoma mansoni. Am J Trop Med Hyg 46:358-65
Wiest, P M; Wisnewski, A V; Johnson, J H et al. (1991) Screening of murine monoclonal antibodies against living schistosomula of Schistosoma mansoni by radioimmunoassay. Int J Parasitol 21:449-54
Wiest, P M; Olds, G R; Bowen, W D (1991) Schistosoma mansoni: protein phosphorylation during transformation of cercariae to schistosomula. Exp Parasitol 73:214-22
Wiest, P M; Kossmann, R J; Tartakoff, A M (1989) Determinants of surface membrane maturation during the cercarial-schistosomula transformation of Schistosoma mansoni. Am J Trop Med Hyg 41:70-7