Telomeres are complex structures at the ends of linear chromosomes of eukaryotes that perform several cellular functions, at least two of which are vital: protection of the chromosome end from degradation and fusion ('capping') and complete replication of DNA sequences at chromosome ends. Studies in several eukaryotic organisms have shown that failure to elongate telomeres or altering telomeric repeat sequences will result in senescence and death. The telomere structure of the malaria vector Anopheles gambiae will be determined molecularly, and the telomere elongation mechanism will be elucidated. To this end, the telomeric region of chromosome 2L will be cloned by using a fortuitous integration event of a D. melanogaster pUChsneo P-element construct that occurred within 0.5 kb of the physical end of the left arm of the second chromosome in A. gambiae. By studying the DNA regions flanking the insert at the proximal and distal end, and by investigating the stability of the integration event of the foreign DNA molecule into the A. gambiae telomeric region, valuable information will be obtained that may be useful in future transformation attempts of A. gambiae. Moreover, using inhibitors of reverse transcriptase which is a crucial step in both proven mechanism of telomere elongation (telomerase and retrotransposition), attempts will be made to inhibit this vital cellular -process in A. gambiae. If successful, there will be novel practical applications for using such inhibitory interference in vector control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI036248-01A1
Application #
2072410
Study Section
Special Emphasis Panel (ZRG5-TMP (01))
Project Start
1995-09-30
Project End
1999-07-31
Budget Start
1995-09-30
Budget End
1996-07-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Walter, M F; Bozorgnia, L; Maheshwari, A et al. (2001) The rate of terminal nucleotide loss from a telomere of the mosquito Anopheles gambiae. Insect Mol Biol 10:105-10
Biessmann, H; Walter, M F; Le, D et al. (1999) Moose, a new family of LTR-retrotransposons in the mosquito Anopheles gambiae. Insect Mol Biol 8:201-12
Biessmann, H; Kobeski, F; Walter, M F et al. (1998) DNA organization and length polymorphism at the 2L telomeric region of Anopheles gambiae. Insect Mol Biol 7:83-93
Kurenova, E; Champion, L; Biessmann, H et al. (1998) Directional gene silencing induced by a complex subtelomeric satellite from Drosophila. Chromosoma 107:311-20
Biessmann, H; Mason, J M (1997) Telomere maintenance without telomerase. Chromosoma 106:63-9
Roth, C W; Kobeski, F; Walter, M F et al. (1997) Chromosome end elongation by recombination in the mosquito Anopheles gambiae. Mol Cell Biol 17:5176-83