The results obtained so far with Ae. aegypti represent the first dynamic approach to determining the fate of amino acids from meal proteins in mosquitoes. Using the methods developed during the last grant period, we are now in a position to probe the metabolic control of amino acid metabolism in more detail and to begin an analysis of metabolic fuel accretion during larval development, as well as, applying these methods to other mosquitoes, such as Culex pipens. The ultimate aim of this project is to define blood meal protein amino acid metabolism in the context of the whole mosquito and to understand, in quantitative terms, how the different metabolic fluxes simultaneously support the gonotrophic cycle after a blood meal and the survival of the female mosquito, because unless she survives the first gonotrophic cycle there would be no opportunity to take a second blood meal and transmit disease. Such an analysis offers a unique opportunity to identify new and unexpected targets for mosquito control. The following specific aims are proposed for the next grant period:
Aim 1 Investigate the metabolic fates of blood meal amino acids in Ae. aegypti females. ? How is the mosquito able to selectively alter the metabolic fate of different amino acids? ? What are the metabolic fates of proline, the major hemolymph amino acid, during blood meal digestion? ? How does the metabolism of ammonia released from amino acid oxidation change during a gonotrophic cycle? Aim 2 Develop quantitative models that accurately describe metabolic flux in Ae. aegypti females. ? What model best describes the time course for amino acid metabolism during the gonotrophic cycle? ? Howcan similar quantitative models be applied to understanding whole mosquito metabolism? Aim 3 Investigate the dynamics of metabolic flux during development in Ae. aegypti. ? How is the metabolism of larvae integrated to ensure the synthesis of energy reserves? Aim 4 Determine metabolic changes that occur in specific tissues ofAe. aegypti females. ? What is the extent of protein turnover under different metabolic conditions? ? Howdoes the metabolism of the fat body and midgut change during the gonotrophic cycle? Aim 5 Investigate the dynamics of metabolic flux during diapause in C.pipiens. ? Howdoes diapause alter sugar metabolism in C.pipiens? ? What is the fate of reserves during diapause in C.pipiens?
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