The long-term aim of this research program is to understand the molecular basis of a host-parasite interaction. Ultimately this information will provide the opportunity to devise strategies to protect the host from infection through the production of vaccines or specific inhibitors to block the unique enzymatic pathways required for the parasite's survival. This proposal aims to: obtain carbohydrate sequence data on these two families (LPG and GIPLS) of cell surface glycoconjugates in amastigotes of the infective strain of L.major, V121.; establish the pattern of expression of LPG and GIPLs during the maturation of the promastigotes into the metacyclic, infective form; define the functional unit(s) of LPG responsible for macrophage binding and examine the possibility that this unit, in different Leishmania sp, shows preference for different macrophage subpopulations; This may shed light on the different tissue tropisms of different Leishmania sp, thus relating LPG to patterns of disease manifestations; examine the biosynthetic pathway(s) of LPG and GIPLs with a view to establishing the relationship between these two classes of glycoconjugates, and in the longer term identify targets for new drug development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI028962-03
Application #
2064756
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1991-09-30
Project End
1995-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Melbourne
Department
Type
DUNS #
City
Melbourne
State
Country
Australia
Zip Code
3010
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Ng, K; Handman, E; Bacic, A (1996) Biosynthesis of lipophosphoglycan from Leishmania major: solubilization and characterization of a (beta 1-3)-galactosyltransferase. Biochem J 317 ( Pt 1):247-55
Kelleher, M; Moody, S F; Mirabile, P et al. (1995) Lipophosphoglycan blocks attachment of Leishmania major amastigotes to macrophages. Infect Immun 63:43-50
Cappai, R; Morris, L; Aebischer, T et al. (1994) Ricin-resistant mutants of Leishmania major which express modified lipophosphoglycan remain infective for mice. Parasitology 108 ( Pt 4):397-405
Ng, K; Handman, E; Bacic, A (1994) Biosynthesis of lipophosphoglycan from Leishmania major: characterization of (beta 1-3)-galactosyltransferase(s). Glycobiology 4:845-53
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Elhay, M J; McConville, M J; Curtis, J M et al. (1993) Identification of truncated forms of lipophosphoglycan in mutant cloned lines of Leishmania major that are deficient in mature lipophosphoglycan. Parasitol Res 79:435-8