Christopher Jagge
Major Professor: Dr. Patricia Pietrantonio
Ph.D. Candidate
"GPRdir1 Transcript Regulation in Female Malpighian Tubules of the Mosquito Aedes aegypti (Diptera: Culicidae)."
The female of the mosquito, Aedes aegypti (L.) is the vector of yellow fever and dengue fever. No vaccine to prevent dengue fever or its associated syndromes has been developed; thus, current dengue disease prevention depends on vector control. The efficacy of traditional insecticides continues to decline as mosquito populations in the USA and worldwide develop resistance. New pesticides with novel modes of action are urgently needed. The pharmaceutical industry has successfully exploited "G Protein" Coupled
Receptors (GPCRs) as drug targets in human medicine. GPCRs in mosquitoes hold promise as novel target sites for the development of unique mosquitocidal compounds. Hormone signaling regulates excess water, ion, and metabolite excretion in blood feeding insects. In response to feeding, hormones released from the brain and other tissues activate GPCRs in the excretory system organs, transducing the signal across the cell membrane and activating effector proteins, such as water and ion channels, thus maintaining salt and water homeostasis. Understanding the physiological process of excretion signaled by these receptors might identify exploitable targets with subsequent identification of synthetic agonists/antagonists -"lead" compounds in the discovery of additional insecticides. Previously, I identified the GPRdir1 receptor cDNA from Aedes aegypti Malpighian tubules. I have determined that the relative transcript abundance significantly fluctuates post-eclosion and in response to a blood meal, indicating a potential mechanism of signaling regulation. A paralog of the DH44. receptor has also been identified. Both receptors are expressed in nervous tissue, but only GPRdir1 is expressed in Malpighian tubules.