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Purpose
The objective of this study is to use genomic/proteomic mass-screens to
identify important mosquito defense factors that will open new avenues
in mosquito innate immunity research, with the ultimate goal of
developing novel mosquito-borne disease control strategies. To achieve
this, an international collaborative mosquito EST project has
accelerated between
Yang-Ming University
and University of Wisconsin. A
further step toward this goal is to establish a bioinformatic system
adopting our ongoing mosquito EST project. A bioinformatic home page of
mosquitoes will include all information from our analyzed data in a
convenient form for mosquito immunity research. Furthermore, proteomic
analysis will provide additional insight regarding gene products
actually associated with different immune responses. Continuing
functional assays of individual cDNAs and proteins will provide a more
thorough understanding of mosquito defense mechanisms. Eventually, one
should be able to utilize this comprehensive knowledge of mosquito
innate immune responses to develop new strategies for blocking the
transmission of mosquito-borne diseases.
Background
Mosquito-borne
diseases are among the most devastating in modern times. Malaria is a
particularly threatening disease that already affects 500 million
people. Diseases caused by mosquito-borne viruses, most importantly
dengue fever, also are on the rise. Unfortunately, the progress of
conventional mosquito-borne disease control has been limited by the
rapidly increasing emergence of multiple drug-resistant pathogens and
insecticide-resistant vectors. Therefore, alternative strategies for
controlling these diseases are desperately needed. Armigeres
sulbalbatus, is not as medically important as
Anopheles gambiae or
Aedes aegypti, but it is the best model system for studies of
melanization immune responses, the predominant defence response against
invading microorganisms, especially malarial parasites. Several cDNA
libraries were constructed from immune-activated Ar. sulbalbatus by
Prof. Bruce Christensen (U. of Wisconsin). A mass EST sequencing program
for all libraries is proceeding under a collaborative agreement between
Yang-Ming University
and
University of Wisconsin. By extending
our EST project to bioinformatic and proteomic analyses, we will
establish a unique mosquito database corresponding to mosquito gene
expression and pathogen invasion. These results also will be valuable
for devising new control strategies for a variety of mosquito-borne
pathogens, e.g., dengue virus control in
Aedes aegypti. For example, "mosquito antibacterial peptides"
already have been shown to reduce malaria development in mosquitoes.
This project should be encouraged by “National Research Program for
Genomic Medicine” because it is an integrated program, involving
genomics, bioinformatics, proteomics and functional assays, and it is an
international collaboration as well. |
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